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Class:NSC 1306 - Introduction to Neuroscience
Subject:Neuroscience
University:Baylor University
Term:Fall 2011
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Neuroanatomy The study of the structure of the nervous system
Neurochemistry The study of the chemical bases of neural activity
Neuroendocrinology The study of interactions between the nervous system and the endocrine system
Neuropathology The study of nervous system disorders
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Neuropharmacology Study of the effects of drugs on neural activity, mostly applied
Neurophysiology

Study of the functions and activities of the nervous system

Comparative approach The study of biological processes by comparing different     species.
Between-Subjects design Experiment involving living subjects where a different group of subjects is tested under each condition
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Within-Subjects design Experiment involving living subjects where the same group of subjects under each condition. 
Independent variable

Difference between experimental groups

Dependent variable The variable that is measured by the experimenter to assess the effect of the independent variable
Confounded Variable

unintended difference between independent variables

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Coolidge effect

A copulating male who becomes unable to have sex with one partner can often recommence copulation with a new partner.

Lordosis

arched-back, rump-up, tail-diverted posture of female rodent sexual recaptivity.

Quasiexperimental studies

studies of groups of subjects who have been exposed to       the conditions of interest in the real world

Case studies

Studies that focus on a single case or subject

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Generalizability

the degree to which their results can be applied to other cases.

Pure research

research motivated primarily by the curiosity of the researcher, it is done solely for the purpose of acquiring knowledge.

Applied research research intended to bring about some direct benefit to humankind
Physiological/Anatomical psychology division of biopsychology that studies the neural mechanisms of behavior through the direct manipulation of the brain in controlled experiments - surgical and electrical methods of brain manipulation are most common. 
Changes in brain functioning cause a change in behavior – so brain is  critical; brain is mind
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Neuropsychology study of the psychological effects of brain damage in human patients, almost exclusive to case studies and quasiexperiments, focus on cerebral cortex. 
Most applied of all disciplines. 
Cerebral Cortex Outer layer of the cerebral hemispheres, most likely damaged by accident or surgery
Psychophysiology

Studies the relation between physiological activity and psychological processes in human subjects. 

Typically noninvasive such as a scalp electroencephalogram (EEG)

Autonomic Nervous System

division of the nervous system that regulates the body’s inner environment.

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Learning/Behavioral neuroscience

Focus on the role of environment in determining behavior.  Influenced by the behaviorist psychologists of the 20th century(Watson, Pavlov, skinner). 

Focuses on the “nurture” side of the nature/nurture dichotomy. Studies how the environment is a primary programmer of the brain’s neural machinery.

Cognitive/Perceptual neuroscience

youngest division of biopsychology, but is currently among the most active and exciting. 

Study of the neural basis of cognition. 

Thinking as opposed to conditioning(language, planning, flexibility) most research involves human subjects and tend to be noninvasive. Essential for understanding higher-order mammals

Cognition a term that generally refers to higher intellectual processes such as thought, memory, attention, and complex perceptual processes.
Comparative/Evolutionary/Ethological/Genetic psychology

deals generally with the biology of behavior, rather than specifically with the neural mechanisms of  behavior.

Compare the behavior of different species in order to understand the     evolution, genetics, and adaptiveness of behavior. 

Evolutionary history has  “shaped”  our human brain Tends to focus on the “nature” side of the nature/nurture dichotomy

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Ethological research study of animal behavior in its natural environment
Scientific inference empirical method that biopsychologists use to study the unobservable. 
They carefully measure key events that they can observe and then use these measures as a basis for logically inferring the nature of events that they can not observe.
Critical thinking process by recognizing the weaknesses of existing ideas and the evidence on which they are based on
Converging operations when the strengths of one scientific approach compensate for          the weakness of others.
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Morgan’s Canon when there are several possible interpretations for a behavioral         observation, the rule is to choose the simplest one. 
Prefrontal lobotomy a surgical procedure in which the connections between the   prefrontal lobes and the rest of the brain are cut as a treatment for mental illness.
Leucotomy Lima used this tool to cut out 6 large cores of prefrontal tissue.  It was inserted 6 times with the cutting wire retracted, after the insertion the cutting wire was extruded and rotated to cut out a core of tissue.
Transorbital lobotomy developed in italy, popularized in the US by Walter Freeman.  Inserting an ice-pick-like device under the eyelid and driving it through the orbital with a mallet, where it is waved back and forth, severing the connection between prefrontal lobes and the rest of the brain.
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Psychosurgery

any brain surgery that is meant for the treatment of a psychological problem

Dualism(Aristotle)

the mind and the body are separate entities

Interactionism

(Cartesian Dualism) the mind and the body are separate, but they   interact in some way.

Epiphenomenalism(Aristotle) the mind and consciousness are incidental bi-products of a functioning human brain.
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Monoism the mind and the body are one and the same - and the brain is really all there is, the mind is an illusion.
Functionalism

The mind is what matters, no matter what produces it, whether that be a  coke machine or brain per say. 

  The machine should be a “black box”.

Philosophical Assumptions neuroscientists make

1.                           Materialism

2.                           Determinism

3.                           Mechanism

4.                           Reductionism

5.                           Emergent Properties

Materialism

Anything other than matter and energy is outside the realm of physics and therefore outside the realm of science generally (including neuroscience)

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Determinism Every even has a cause.
 These causes can be determined, discovered, cataloged, and used to predict future events.
If events were not determined, then science would be a poor career choice because there would be no certainty. FUNDAMENTAL to science.
Distal causation

distant, remote, complex to understand

Proximal causation immediate causes: Stimuli and environment.
Mechanism Causes have a Physical basis. 
Only physical determinants of behavior can be quantified, observed, and measured. 
The universe behaves in a regular and orderly manner - stuff doesn’t just happen.
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Ultimate causation Teleology
-  Why does this happen?
-  Neuroscience can only answer some of these ?’s
-  Why are we here?
-  We cannot answer why because science is not adept at answering teleology questions.

Reductionism Complex phenomena can often be “reduced” to simpler physical  processes.  
Each finer level of analysis relies on more basic, fundamental, more molecular processes.  
Explanations tend to move from the molar(behavioral) to the molecular (anatomy, physiology, neurochemistry).
Empiricism A method of obtaining information by observation and experimentation(data).
These data are used to generate explanations, hypotheses, and theories. The hypotheses and theories are then tested.
Predictive theories are retained, faulty ones are modified or discarded.
Scientists replicate the work of others and either verify it or criticize it. - Theories are then corrected.  Science self corrects.
Natural History Understanding the earth, and the history of life on earth, from a      scientific perspective
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Cosmology Theories of the origin of the earth, of life, of the universe.
Evolution The theory of evolution is a comprehensive, integrative, scientific account of  the origin of species
Genetics

The biological mechanisms that code for an organisms structure and  function, including reproduction.

Other theories of evolution had been proposed earlier, but Darwin’s was novel because of the mechanism: Natural Selection

Neo-Darwinian Theory Basic ideas of Darwinian Evolution intact.
Incorporates modification based on recent evidence(eg. Gould’s notion of “punctuated equilibrium”).
Incorporates modern genetic theory, Mendel’s work was done more than 30 years after “Origin of Species”, well after Darwin’s death). 
Modern research is biochemical genetics
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Divisions of Neo-Darwinian Theory of Evolution

1.  Environment

2.  Life

3.  Heredity

4.  Continuity

5.  Sex

6.  Variability

7.  Natural Selection

Neo-Darwin Evolu: Environment life exists in an uncaring environment.
Environment provides ecological niche
Neo-Darwin Evolu.: Life

Some groups of chemicals have the ability to self replicate.

On earth, these chemicals are DNA.

With unlimited resources, life replicated unchecked.

Neo-Darwin Evolu.: Heredity Characteristics are passed from parent to off-spring.DNA codes for these characteristics, and is passed from parents to off-spring at conception.
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Neo-Darwin Evolu.: Continuity

Organisms related not only to parents, but to every other living organism.

 Notion of “Common Ancestor”. 

  Some organisms have recent common ancestors(humans and monkeys), others more remote(humans and armadillos).

  Doesn’t mean one organism “evolved from” another.

Neo-Darwin Evolu.: Sex Genes perpetuate themselves through sexual reproduction.  Not all members of a species reproduce with the same success (or with the same frequency). 
Most organisms reproduce in ever-increasing numbers.
Neo-Darwin Evolu.: Variability

Both parents contribute equally to genetic makeup of off-spring.  However, the genetic “mixture” is different each time (that is, the 50% from father is randomly determined for each organism)  

Some errors get  introduced during reproductions (eg. Genetic mutations). 

 Some combinations of genes are more successful than others.  Some isolated populations change enough over time that they cannot interbreed: Speciation

Neo-Darwin Evolu.: Natural Selection Usually, resources are limited: Selectivepressure
 Organisms must compete for limited resources.  
Some members of a species are better able to compete: Survival of the fittest.
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Fitness Fitness is defined as an organism’s ability to survive and reproduce.  
“Success” is the organism’s ability to pass on its genes to future generations.
Some members of a species are better able to compete: survival of the fittest. 
Richard Dawkins’ The Selfish Gene--the idea of inclusive fitness.  
Fitness only has meaning in the context of specific selective pressures(environments), as an environment changes, so does fitness.  
Fitness doesn’t mean better, just better adapted to the environment, and evolution doesn’t mean progress or           improvement, it only means that a species has changed in response to changes in the environment.
It is meaningless to speak of organisms being “more highly evolved”. 
Reasons why Darwinian Evolution is so controversial

1.  Places humans squarely within the realm of all organisms, not “above” the collection

2.  Removes humans from being a “special” creature (humans can still be unique)

3.  Often misunderstood as an attack on religious explanations, or as being incompatible with theology or religion -- not true

4.  Fails to address the ultimate “why” question -- our purpose for being(all scientific theories fail at this)

Behavioral Genetics

A technique for assessing the relative contribution of genetic and   environmental factors in behavior.

 Assumes behavior has causes that can be grouped into 2 broad categories:
behavioral genetics assumes behavior has causes that can be grouped into 2 broad categories:

1.    Genetic Factors: Not “a gene” but all the genetic factor which contribute to the behavior in question.

2.     Environmental Factors: Everything that one experiences in one’s life.

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Genetic Factors

The total contribution of genetic factors to the specific behavior is question is expressed by a single number called a heritability coefficient (h^2)

Heritability The proportion of variability in a given population which can be attributed to genetic factors.
Environmental Factors

Shared Environmental Influence (Es) - influences shared by all members of a family


Unique Environmental Influence (ENS) - All other enviro influences

Main problem in assessing the contribution of genetic and environmental influences Most individuals who are related genetically also share environmental  background. 
One needs to find individual who share genetic influences,environmental influences, both and neither, and compare their behavior.
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3 major conclusions about Behavioral Genetics

1.  The degree of Genetic Influences typically ranges between .4 and .7, roughly half of the variability can be attributed to genetic factors

2.  Effects of the Family Environment is minimal Es<.1, usually close to 0

3.  A significant proportion of behavior can be attributed neither to genetic factors nor the family, and is presumably caused by unique environmental factors. (Ens ~ .5)  Friends may be the most important environmental influence.

Heritability Formula VB = h2 + (ES + EU) + h2 x E(S+U) + ε
Behavioral Variance (=) is composed of genetic, environmental, and g X e influences, plus some Error -- because we don’t make perfect predictions.
Central Nervous System(CNS) Involves the brain and the spinal cord.
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Peripheral Nervous System (PNS) Located outside of the skull and spine.
Serves to bring information into the CNS and carry signals out of the CNS. 
The two PNSs include: Somatic Nervous system (afferent(sensory) and efferent nerves(motor), sensory and motor respectively) and Autonomic Nervous System (efferent, sympathetic and parasympathetic nerves)
Autonomic Nervous System All nerves are efferent(info.out).  
Sympathetic and parasympathetic nerves generally have opposite effects. 
2 stage neural paths, neuron exiting the CNS(presynaptic) synapses on a second stage neuron, in a ganglion, before ending on the target organ(postsynaptic).
Sympathetic nerves

located in the Thoracic and lumbar regions of the spine. 

  Control your “fight or flight” response.  

They are second stage neurons, ganglia, are far  from the target organ.

Parasympathetic nerves located in the Cranial and sacral regions of the spine.  
Meant to “Rest and restore”(returns body to normal after being altered by sympathetic stimulation. 
Second stage, ganglion, located near the target organ.
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Autonomic Nervous System Controls

Heart (SNS up; PNS down); 

BP (SNS up; PNS down); 

Cortisol levels (SNS up);

 Pupil size;

 Blood flow to sex organs and orgasm;

 Blood to gut (SNS up; PNS down);

 Sweating (SNS up); 

Micturition(need both SNS and PNS); 

Glycogen Release (SNS up)

3 meninges covering the CNS in bone

1.  Dura mater - tough outer membrane

2.  Arachnoid membrane - web-like

3.  Pia mater - adheres to CNS surface

Cerebrospinal fluid (CSF) fluid that serves as a cushion; also has ionic function and     acts like plasma
Ways you protect your brain

Chemical protection - The Blood-Brain Barrier

 Physical protection - Skull; Meninges; Cerebrospinal fluid.

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: Blood-Brain Barrier

unfenestrated endothelial cells of capillary walls prevent entry of     many larger, non-fat soluble molecules - unlike outside the brain.

Golgi Stain allows for visualization of individual neurons (light microscope)
Nissl stain

selectively stains cell bodies (light microscope)

Electron microscopy

provides information about the details of neural structure - uranyl & osmium stains (heavy metals: electron beam dense)

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Areas of the Spinal Cord

Gray matter(inner component, primarily cell bodies)

 White matter(outer area, mainly myelinated axons)

 Dorsal(afferent, sensory)

 Ventral(efferent, motor).

forebrain

midbrain

hindbrain

spinal cord

telecephalon (cerebral hemispheres)

diencephalon

mesencephalon (midbrain)

metencephalon

myelencephalon (medulla)

spinal cord
Myelencephalon

Medulla

Composed largely of tracts

 Origin of the reticular formation

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Metencephalon Many tracts
 Pons(ventral surface)
Cerebellum(coordination)
1. pons

2. reticular formatoin

3. medulla

4. cerebellum
Mesencephalon Midbrain
Tectum(superior colliculi, inferior colliculi)     Tegmentum(Reticular formation, Cerebral aqueduct, Periaqueductal gray, substantia nigra, Red Nucleus)
1.  superior colliculus
2.  periaqueductal gray
3.  mesencephalic reticular formation
4.  cerebral aqueduct
5.  red nucleus
6.  substantia nigra
7.  tectum
8.  tegmentum
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Diencephalon

Thalamus(Massa intermedia, lateral geniculate nuclei, medial geniculate nuclei, ventral posterior nuclei)

Hypothalamus(mammillary bodies)

 Optic chiasm

Pituitary gland.

Telencephalon Cerebral Cortex
Convolutions serve to increase surface area
 Longitudal fissure - a groove that separates right and left hemispheres
Corpus callosum - largest hemisphere-connecting tract
4 lobes of the Cerebral Cortex

1.  Frontal (Future planning, speech production, behavior inhibition

2.  Occipital (vision)

3.  Parietal (touch, cross-modal matching, language, spatial skills

4.  Temporal (Language reception, hearing)

Limbic System

Subcortical structure

 Telencephalon

 Regulation of motivated behaviors

  Includes: Mammillary bodies, hippocampus, amygdala, fornix,             cingulate, septum.

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Basal ganglia motor system Subcortical structure
 Facilitate movement &/or suppress movement
Includes: Amygdala, striatum (caudate nucleus+putamen), globus  pallidus.
Contrast X-rays inject something that absorbs X-rays less or more than surrounding tissue, such as cerebral angiography
X-ray computed tomography (CAT or CT)

Computer-assisted X-ray procedure

 Provides 3-D representation of the brain

The brain is viewed in slices

 Good  resolution(anatomy only)

 Shows pathology, bleeds, deformity very well

 Resolution: couple of mm.

Magnetic Resonance imaging (MRI)

High resolution images

 Constructed from measurements of waves that hydrogen atoms emit when activated within a magnetic field
High field strength magnet - cooled by liquid gas

 Cylinder, noise, constraint stress

 Very precise view of normal and abnormal brain
 Can also be used to study metabolism.

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Positron emission tomography (PET)

Provides images of brain activity

Scan is an image of levels of radioactivity in various parts of one horizontal level of the brain

A radiolabeled substance is administered by injection prior to the scan

 As the iostope decays the PET detects the decay and plots anatomy and metabolism.

Functional MRI (fMRI)

Provides images of brain structure and activity

 As with MRI uses strong magnetic field

 Structure is imaged using waves emitted by hydrogen ions acting in an intense magnetic field

Function is imaged using signal created from interaction between oxygen and iron in the blood

 Fast but not as fast as we would like(on the order of seconds)

Magnetoencephalography (MEG) A measure of neural activity
 Measures changes in magnetic fields on the surface of the scalp(created by underlying patterns of neural activity)
 Fast temporal resolution - sub-seconds resolution.
Transcranial magnetic stimulation (TMS)

NOT a measure of neural activity, but  provides an experimental probe to alter neural activity

TMS applies a brief, strong magnetic field that alters neural activity(can either activate or deactivate brain structures, observe changes in behavior, or create “reversible Lesions” which mimic lesions.

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- Scalp electroencephalography (EEG) measure of gross elecrtical activity of the brain
 uses electrodes attached to the scalp
 Wave for assessment(records brainwaves, and when your brainwaves cooperate then you are rewarded with a positive   feedback loop.  Brain is gently nudged into behaving in a new way).
Electromyography (EMG)

the technique of measuring the voltage generated by muscle           activity

 Indicates tension of muscles(level of contraction)

Measures of electrodermal activity Skin conductance level (SCL):measure of the background level of skin conductance that is associated with a particular situation
Skin conductance response(SCR): measure of the transient changes in skin conductance that are associated with discrete experiences.  Skin conductance from emotional arousal.
Electrocardiogram (ECG or EKG)

 Measures cardiovascular activity such as heart rate,   blood pressure, and blood volume

 Often used to link physiological changes with emotional state - level of arousal.

 

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Stereotaxic surgery

requires use of stereotaxic atlas to locate brain structures like a        road map, and a stereotaxic instrument

 - two part tool:

1. a head holder, which firmly holds the patients brain in the correct position and orientation

2. and an electrode holder, which hold the device to be inserted.

Aspiration lesions used when a lesion is to be made in an area of cortical tissue that is accessible to the eyes and instruments
Cortical tissue is suctioned off through a finetipped handheld glass pipette
Because Underlying white matter is slightly more resistant to suction, a surgeon can delicately peel off the layers of cortical tissue from the surface, leaving the underlying white matter and major blood vessels undamaged
Lesion methods Bilateral and unilateral lesions
Several procedures each require careful interpretation of effects.
1.  aspiration lesions
2.  radio-frequency lesions
3.  knife cuts
4.  cryogenic blockade
Radio-frequency lesions Small subcortical lesions made by passing radio-frequency current through the target tissue from the tip of a stereotaxically positioned electrode
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Knife cuts Cutting is used to eleminate conduction in a nerve or tract
. Cryogenic blockade using an implanted cryoprobe with flowing coolant fluid to cool the neurons to the point of not firing
Electrical stimulation Lesioning can be used to remove, damage, or inactivate a     structure.
Electrical stimulation may be used to “activate” a structure.  Application of drugs to brain sites-stimulate and inhibit.  Stimulation of a structure may have an effect opposite to that seen when the structure is lesioned.
Invasive electrophysiological recording methods 1.  Intracellular unit recording

2.  Extracellular unit recording

3.  Multiple-unit recording

4.  Invasive EEG recording
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Intracellular unit recording moment by moment record of the graded fluctuations of one neurons membrane potential.
Extracellular unit recording a record of the firing of a neuron but no info on the membrane potential, electrode is placed beside a neuron so that when the neuron fires, an electrical disturbance
Multiple-unit recording The electrode tip is larger than the microelectrode used in extracellular unit recording, allowing it to pick up signals from many neurons and slight shifts in its position due to movement have little effect on the overall signal. 
Produces a graph of the total number of recorded action potentials per unit of time
. Invasive EEG recording

EEG signals are recorded through a large implanted electrodes rather than on the scalp

Cortical EEG signals are frequently recorded through stainless steel skull screws, whereas subcortical EEG signals are recorded through stereotaxically implanted wire electrodes.

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Routes of drug administration 1. Fed to the subject
 2. injected through a tube into the stomach(intragastrically); or 3. injected hypodermically into the peritoneal cavity of the abdomen, into a large muscle, into fatty tissue beneath the skin, or into a large surface vein. 
For drugs that do not readily pass the blood-brain-barrier, a fine, hollow tube known as a cannula is stereotaxically inserted into the brain
Selective chemical lesions

Make a more selective lesion by injecting neurotoxins that have an affinity for certain components of the nervous system.  

2-Deoxyglucose Technique of measuring chemical activity of the brain

Inject animal with radioactive 2-DG and allow it to engage in behavior of interest

 The subject is killed and brain slices are subject to autoradiography; coated with photographic emulsion, stored in the dark, and developed like film.

The areas of the brain that absorbed high levels of 2-DG during the test appear as black spots on the slides.  

The density of the spots are then color coated.

Cerebral Dialysis measures extracellular concentration of specific chemicals in live animals.
Implant a fine tube with a short semipermeable section, this section is positioned in the brain structure of interest so that the extracellular chemicals diffuse into the tube.
The chemicals are then frozen for later testing or directly put in a chromatograph
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Locating Neurotransmitters and receptors in the brain Dye or radioactive labels used to visualize the protein of interest. 
1.  Immunocytochemistry 

2. In situ hybridization


 
Immunocytochemistry

labeling certian neuroproteins’ antibodies with a dye or radioactive element and then exposing slices of brain tissue to the labeled antibodies

 Regions of dye accumulation in the brain mark the locations of the target neuroprotein

In situ hybridization

first obtain hybrid RNA that has a base sequence complementary to that of the mRNA of the target protein.

The hybrid RNA are labeled with dye or radioactive element.

Brain slices are then exposed to the labeled RNA, they bind to the mRNA, thus marking the location of neurons that release the target.

Gene knockout techniques creating organisms that lack a gene. 
Subjects missing a given gene can provide insight into what the gene controls.
Knockout mice. 
The results are difficult to interpret since most behavior is controlled by many genes and removing one gene may alter the expression of others, including compensation for the missing gene.
Antisense drugs block expression of a gene.
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Gene replacement techniques Pathological genes from human cells can be inserted into mice.  Mice that contain genetic material of another specie are called transgenic mice.  
Behavioral paradigm

A single set of procedures developed for the investigation of a         particular behavioral phenomenon.

Humans in Natural experiments

Time consuming: only conducted on a small portion of  those with brain damage.

Assists in diagnosing neural disorders.

Serves as a  basis for counseling/caring for patients.  Provides information on effectiveness and side effects of treatment.  

Single-test approach to neuropsychological testing Used to differentiate brain damage from functional (psychological) cause. 
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Standarized-Test-Battery approach to neuropsychological testing

Same goal as single test approach, but involved sets of tests rather than a single test.

 Halstead-Reitan: preformed poorly by brain damaged patients.

Customized-Test-Battery approach to neuropsychological testing

Predominant approach

 Subjects given a common battery of test and depending on the general diagnosis(such as memory problem) a customized 2nd set of test would be given to assess the specifics.

Tests of the common neuropsychological test battery 1.  intelligence

2.  memory

3.  language tests

4.  language laterlization
Intelligence test of the common neuropsychological test battery Wechsler Adult Intelligence Scale
WAIR, an IQ test
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Memory test of the common neuropsychological test battery
digit span subtest - ids the longest sequence of random digits that a patient can repeat correctly. 
Language test of the common neuropsychological test battery to find problems of phonology, syntax, semantics
Language laterlization test of the common neuropsychological test battery used to ID language-dominant hemisphere
Sodium amytal anesthetizes one hemisphere
Dichotic listening - ear contralateral to dominant hemisphere shows superior hearing ability
Tests of specific neuropsychological function 1.  Memory

2.  Language

3.  Frontal-Lobe Function
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Memory tests of specific neuropsychological function
Repetition Priming Test
4 questions must be answered following a positive on the memory section of the common test battery
1.  short-term, long-term, or both?
2.  Anterograde or retrograde?
3.  Semantic(knowledge of the world) or episodic(personal experience)?
4.  Explicit(memories in which the patient is aware and can express verbally) or implicit(improved performance of the patient w/o the patient being conscious of them)? 

Repetition Priming Test
Shown a list of words, then at a later time they are asked to complete word fragments, many of which are from the initial list.
 
Language tests of specific neuropsychological function problems of phonology, syntax, or semantics
Frontal-Lobe Function tests of specific neuropsychological function Wisconsin Card Sorting Task - each card has one, two, three, or four identical symbols; patients are given 4 unique cards; the patients are asked to sort a deck without knowing the sorting order, once a card is placed, the tester gives a yes or no, once the patient learns the pattern they shift the required sorting order
Frontal lobe damage causes the continued sorting principle for 100 or more trials after it has become incorrect
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Assumptions of cognitive neuroscience 1.  Each complex cognitive process results from the combined activity of simple cognitive processes(constituent cognitive processes)

2.  Each complex cognitive process is mediated by neural activity in a particular area of the brain(specificity of effect.) But, all areas are connected and damage in one can affect others(global effects)

Main goal of cognitive neuroscience

To identify the parts of the brain that mediate various constituent cognitive processes.

 

Paired-image subtraction technique

Compare PET or fMRI images during several different cognitive tasks, you look for areas that are different with different tasks.

 

Biopsychological Paradigms of Animal Behavior Procedures developed for the investigation of a particular behavioral phenomenon
Assess behavioral function on common problem-focused behaviors in humans and non-humans
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Paradigms for assessment of species-common behaviors (4 tests) Behaviors that are displayed by virtually all members of a species, or at least by all those of the same age and sex.
1.  open field test
2. Tests of aggressive and defensive behavior
3.  Tests of Sexual behavior 
4.  Tests of behavioral inhibition
 
Open-Field test

a subject is placed in a large, barren chamber, an its activity is recorded.

Low activity and high poop count is frequently used as an indicator of fear

Fearful rats are highly thigmotaxic(rarely venture away from the walls of the test chamber and rarely engage in activities such as rearing and grooming)

 

Tests of Aggressive and defensive behavior

Aggression and defensive behavior can be observed and measured during combative encounters between the dominate male and a smaller male intruder. <----- Colony-intruder paradigm.  

Piloerection, lateral approach, and flank and back biting indicate aggression

freezing, boxing, and rolling over indicate defensive

Elevated plus maze(4 armed plus shape, 2 sides have walls, 2 don’t) commonly used to study anxiolytic drugs.

Tests of sexual behavior in animal behavior

Intromission(8===D <>). 

Measure the number of mounts required to achieve intromission, the number of intromissions required to achieve ejaculation, and the interval between ejaculation and the reinitiating of mounting. 

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Traditional Conditioning Paradigms 1. Pavlovian conditioning
2. Operant conditioning
1. Pavlovian conditioning pairing an unconditioned stimulus with a conditioned stimulus, e.g. Pavlov’s dogs
Operant conditioning reinforcement and punishment
e.g. self-stimulation paradigm<animal presses lever to deliver stimulation to the pleasure centers of the brain>
Conditioned Taste Aversion Pairing something that makes an animal ill(emetic) with a taste, challenged existing assumptions about conditioning(not always a gradual process, showed that temporal contiguity is not essential for conditioning<rats became averted by the taste even if illness hasn’t occured yet>, and finally it challenged the view that conditioning proceeds in basically the same manner regardless of the particular stimuli and responses under investigation) , animals appear prepared to associate tastes and illness
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Radial Arm Maze Spatial learning
Morris Water Maze Spatial learning
rat must find platform in an opaque pool
Complex cognitive task preformed under sever stress
Patton & Stanford: effects of Prozac on fetal development.
Green Florescent Protein (GFP)

Exhibits bright green fluorescence when exposed to blue light. Variants of the gene for GFP can express other colors. 

These GFP genes can be inserted into DNA of neurons - color can then be viewed when targeted neuronal genes are expressed giving us a BRAINBOW!!!

Antidromic conduction If electrical stimulation of sufficient intensity is applied to the terminal end of of an axon, an action potential will be generated and will travel along the axon back to the cell body.
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Orthodromic conduction natural direction of Action potentials
nodes of Ranvier

The gaps between adjacent myelin segments

 ions can only pass here on the axon.

 

Saltatory conduction transmition of action potentials in myelinated axons.
 the AP jumps along the axon from node to node
Directed synapses synapses at which the site of neurotransmitter release and the site of neurotransmitter reception is in close proximity.  
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Nondirected synapses  synapses at which the site of release is at some distance from the site of reception.  
Neuropeptide

short amino acid chains comprising of 3-36 amino acids


 short proteins.

 

(Fill in the blank) cytoplasm, synaptic vesicles, Golgi complex Small molecule neurotransmitters are typically synthesized in the __________ of the terminal button and packaged in _____________ by the buttons _________.
Coexistence many neurotransmitters contain 2 NTs
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Exocytosis NT release
ligand any molecule that binds to another
Autoreceptors
Acetylcholinesterase enzyme that breaks down acetylcholine
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Gap junctions narrow spaces between neurons that are bridged by fine tubular channels, called connexins, that contain cytoplasm
Amino Acid NTs

Glutamate, aspartate, glycine, gama-aminobutyric acid (GABA)

 

Glutamate

most prevalent excitatory NT in the mammalian central nervous system

 

Monoamine NTs

slightly larger than amino acid NTs and their effects tend to be more diffuse, also released diffusely.  Dopamine, epinephrine, norepinephrine, and serotonin.

 

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2 groups of MAONT

Catecholamines (Dopamine, norepinephrine, epinephrine) Synthesized from l-dopa, Indolamines(serotonin, synthesized from tryptophan)

Acetylcholine

small molecule NT at neuromuscular junctions, at many of the synapses in the ANS, and at synapses in several parts of the CNS.  Released by cholinergic neurons.

Soluble-gas NTs

Nitric Oxide and carbon monoxide.

Produced in cytoplasm, diffuse out of neuron into extracellular fluid and then into nearby cells.

Stimulate a second messenger.  Last a few seconds. 

 Involved in retrograde transmission(send signals from post to presynapses)

Endocannabinoids

Nts that are similar to THC.

Anandamide.

released from dendrites and cell body, effect presynaptic neurons, inhibit these neurons synaptic transmission.

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Neuropeptide transmitters

Pituitary peptides(hormones released by pituitary), hypothalamic peptides, brain-gut peptides, opioid peptide, miscellaneous peptides.

Agonist facilitate the effects of a particular NT
Antagonists

drugs that inhibit the effects of a particular NT. 

Receptor blocker

Enkephalins endorphin from opioid
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Oral ingestion of drugs  influenced by digestive system, small molecules act more rapidly, unpredictable
Inhalation

more direct route, rapid effects.

difficult to regulate a dose.

 

Mucous membranes

nose, mouth, rectum.

 very rapid

Injection  subcutaneous, intramuscular, intravenous.
 fast and direct.
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Metabolic tolerance a decrease in the amount of drug due to metabolism
Functional tolerance  a decrease in drug effect because of changes in receptor sensitivity
Contingent tolerance demonstrations that tolerance develops only to a drug effects that are actually experienced.
Situational specificity (conditioned drug tolerance)

tolerance effects are maximally expressed only when a drug is administered in the same situation in which it has been previously administered

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Tobacco 2nd most widely used psychoactive drug behind caffeine.  Nicotine is the major ingredient.
Contains 4000 different compounds with approx. 1500 coming from additives, pesticides and other organic/metallic compounds.
Compounds include CO, ammonia, hydrogen cyanide, nitrites, and radioactive compounds.
 43 known or suspected carcinogens are found in cigarette smoke.
Nicotine

Lethal dose of nicotine is 60mg.

 Typical cig will deliver .05-2.5mg.

 Reaches the brain quickly and facilitates the release of dopamine in the nucleus accumbens(group of cell bodies in the ventral striatum<major target of the dopamine system>).  

Buerger’s disease. 

Consequences of long term use include an increase risk of: cancer, emphysema, and respiratory infections.

Alcohol

Depressant, exact neural mechanism unknown, acts on GABA, glutamate, dopamine, and serotonin systems. 

 Results of chronic use: blackouts, reduced brain activity in parietal and frontal regions, and Korsakoff’s syndrome.

Marijuana

cannabis sativa, wild cannabis not very potent, historically used as an analgesic, hypnotic, and anticonvulsant, THC acts at the cannabinoid receptor, anandamide seems to be an endogenous cannabinoid.  

May play a role in pain and memory.

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Opiates opium is found in the opium poppy, the most notable psychoactive ingredient is morphine, Opiates mediate pain perception, anxety, sedation and pleasure, 
Euphoria mediated by opioid auction on the VTA.
Intracaranial self-stimulation (ICSS)

Discovered in the 1950s by james olds and peter milner.

brief bursts of weak electrical stimulation to specific pleasure centers.

  These centers of pleasure also mediate the pleasurable effects from eating, drinking, and sex. 

  Similar to lever pressing for rewards. 

 

Mesotelencephalic Dopamine System

dopaminergic neurons the project from the midbrain to the telncephalon. 

  Agonists increase while antagonists decrease dopamine. 

  Damage to MDS structures disrupts ICSS.

Dopamine and Human Addicts  Imaging studies show involvement of dopamine in addiction. 
Dopamine activity is muted in drug addict individuals. 
 In the presence of drug stimulation, the mesotelencephalic dopamine system became hyperactive.
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Epilepsy

Description: Intermittent disruption of brain function produced by a sudden, intense, uncontrolled discharge of neurons. 


  Cause:  Varied: Congenital, stroke, tumors, trauma, poisioning. 

  For all types of epilepsy, the concordance rate is .44 for monozygotes and .10 for dizygotes.  


Treatment: surgery, pharmaceutical interventions.

 

Generalized seizures no localized onset, bilateral symmetry, most common generalized seizures are termed grand mal and petit mal.
Petit mal seizures are characterized by a 3-per-second-spike and wave discharge.
Partial Seizures Have a clear point of origin.
 Asymmetrical.
 Divided into simple and complex.
 simple partial seizures have motor and/or sensory symptoms (jacksonian march).
complex partial seizures have psychological symptoms and may develop into a psychomotor attack.
Parkinson’s Disease Movement disorder characterized by: tremors and stiffness; tremors are pronounced during inactivity; muscle rigity; difficulty initiating movement; slowness of movement; mask-like face...
 

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Cause of Parkinson's Disease  No single cause; Infections, strokes, tumors, neurotoxic events, trauma, and genes have all been implicated, associated with loss of dopamine neurons in substantia nigra.  Early onset PD has a stronger genetic component than late, concordance rates among twins are relatively low, chromosome 4 has been implicated, obviously, there is a strong environmental component.
Treatment for Parkinson's Disease Treatment: Pills, Surgical lesions, deep brain stimulation.
Cause of Huntingtons Disease Dominant Huntington gene that produces the huntington protene, if you have it you will get it, 50% chance of passing it on. 
Huntingtons Disease Progressive terminal disorder of motor and intellectual function.
Characterized by: chorea(difficulty speaking), difficulty swallowing, personality changes and withdrawal from social activities, paranoia, hallucinations, psychosis, depression, memory loss, poor decision making.
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Treatment for Huntingtons Disease

NONE!

Multiple Sclerosis A progressive disease of the CNS myelin.  
Symptoms: dizziness and loss of balance, fatigue, hand or leg weakness, inflammation of nerves in the eye, localized tingling or numbness, visual impairments, including blurred or double vision.
Cause of Multiple Sclerosis Environmental, Genetic(monozygotes 30% vs 5% for dizygotes), Autoimmune response, viral trigger
Treatment for Multiple Sclerosis

No cure, Pills, Rehab.

 

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Alzheimer’s Disease
Cause of Alzheimer’s Disease Most common cause of dementia, likelihood of developing it increases with age.
Progressive, with early stages characterized by confusion and a selective decline in memory. 
Must observe neurofibrillary tangles and amyloid plaques to be sure it was Alzheimer’s.  
Several genes ID’d as involved w/ early onset AD.
All affected genes are involved in synthesis of amyloid or tau, a protein found in the tangles.  Not clear what comes first- plaques or tangles. 
Decline in acetylcholine levels.
Kindling model of epilepsy

A series of periodic brain stimulations eventually elicts convulsions - the kindling phenomenon (Neural changes are permanent).  Convulsions are similar to those seen in some forms of human epilepsy - but they only occur spontaneously if kindled for a very long time.  

Comparable to the development fo epilepsy seen following a head injury

MPTP model of Parkinson’s

 Synthetic heroin produced symptoms of PD, contained MPTP(causes cell loss in the substantia nigra, like that seen in PD).  Deprenyl can slow the progression of PD.

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Anterograde Neuron regeneration

Between cut and synaptic terminal.

Cut off from metabolic center, swells and breaks off within a few days

Retrograde Neuron degeneration Cut and cell body
Progresses slowly, may survive if regenerating axon makes new synaptic contact
Neural regeneration doesn’t occur successfully in mammals and other higher vertebrates.
capacity for accurate axonal growth is lost in maturity.  Virtually nonexsistent in the CNS and unlikely, but possible, in the PNS
Schwann cells promote neural regeneration.
 neurotropic, CAM’s provide a pathway.
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Oligodendroglia actively block regeneration
Cognitive reserve

education and intelligence - thought to play an important role in recovery of function - may permit cognitive tasks to be acomplished in new ways.

 

How to reduce brain damage by blocking neurodegeneration

Apoptosis inhibitor protein.

 Nerve growth factor(blocks degenerationon damaged neurons).

Estrogens - limit or delay neuron death

Promoting regeneration CNS neurons can be induced to regenerate.
Eliminate inhibition of oligodendroglia and provide schwann cells.
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Promoting recovery by neurotransplantation

Fetal tissue(fetal substantia nigra cells used to treat MPTP-treated monkeys, treatment was successful, limited success in humans)


 Stem cells(rats w/ spinal damage “cured”, but much more research is needed.)

 

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List View: Terms & Definitions

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 NeuroanatomyThe study of the structure of the nervous system
 NeurochemistryThe study of the chemical bases of neural activity
 NeuroendocrinologyThe study of interactions between the nervous system and the endocrine system
 NeuropathologyThe study of nervous system disorders
 NeuropharmacologyStudy of the effects of drugs on neural activity, mostly applied
 Neurophysiology

Study of the functions and activities of the nervous system

 Comparative approachThe study of biological processes by comparing different     species.
 Between-Subjects designExperiment involving living subjects where a different group of subjects is tested under each condition
 Within-Subjects designExperiment involving living subjects where the same group of subjects under each condition. 
 Independent variable

Difference between experimental groups

 Dependent variableThe variable that is measured by the experimenter to assess the effect of the independent variable
 Confounded Variable

unintended difference between independent variables

 Coolidge effect

A copulating male who becomes unable to have sex with one partner can often recommence copulation with a new partner.

 Lordosis

arched-back, rump-up, tail-diverted posture of female rodent sexual recaptivity.

 Quasiexperimental studies

studies of groups of subjects who have been exposed to       the conditions of interest in the real world

 Case studies

Studies that focus on a single case or subject

 Generalizability

the degree to which their results can be applied to other cases.

 Pure research

research motivated primarily by the curiosity of the researcher, it is done solely for the purpose of acquiring knowledge.

 Applied researchresearch intended to bring about some direct benefit to humankind
 Physiological/Anatomical psychologydivision of biopsychology that studies the neural mechanisms of behavior through the direct manipulation of the brain in controlled experiments - surgical and electrical methods of brain manipulation are most common. 
Changes in brain functioning cause a change in behavior – so brain is  critical; brain is mind
 Neuropsychologystudy of the psychological effects of brain damage in human patients, almost exclusive to case studies and quasiexperiments, focus on cerebral cortex. 
Most applied of all disciplines. 
 Cerebral CortexOuter layer of the cerebral hemispheres, most likely damaged by accident or surgery
 Psychophysiology

Studies the relation between physiological activity and psychological processes in human subjects. 

Typically noninvasive such as a scalp electroencephalogram (EEG)

 Autonomic Nervous System

division of the nervous system that regulates the body’s inner environment.

 Learning/Behavioral neuroscience

Focus on the role of environment in determining behavior.  Influenced by the behaviorist psychologists of the 20th century(Watson, Pavlov, skinner). 

Focuses on the “nurture” side of the nature/nurture dichotomy. Studies how the environment is a primary programmer of the brain’s neural machinery.

 Cognitive/Perceptual neuroscience

youngest division of biopsychology, but is currently among the most active and exciting. 

Study of the neural basis of cognition. 

Thinking as opposed to conditioning(language, planning, flexibility) most research involves human subjects and tend to be noninvasive. Essential for understanding higher-order mammals

 Cognitiona term that generally refers to higher intellectual processes such as thought, memory, attention, and complex perceptual processes.
 Comparative/Evolutionary/Ethological/Genetic psychology

deals generally with the biology of behavior, rather than specifically with the neural mechanisms of  behavior.

Compare the behavior of different species in order to understand the     evolution, genetics, and adaptiveness of behavior. 

Evolutionary history has  “shaped”  our human brain Tends to focus on the “nature” side of the nature/nurture dichotomy

 Ethological researchstudy of animal behavior in its natural environment
 Scientific inferenceempirical method that biopsychologists use to study the unobservable. 
They carefully measure key events that they can observe and then use these measures as a basis for logically inferring the nature of events that they can not observe.
 Critical thinkingprocess by recognizing the weaknesses of existing ideas and the evidence on which they are based on
 Converging operationswhen the strengths of one scientific approach compensate for          the weakness of others.
 Morgan’s Canonwhen there are several possible interpretations for a behavioral         observation, the rule is to choose the simplest one. 
 Prefrontal lobotomya surgical procedure in which the connections between the   prefrontal lobes and the rest of the brain are cut as a treatment for mental illness.
 LeucotomyLima used this tool to cut out 6 large cores of prefrontal tissue.  It was inserted 6 times with the cutting wire retracted, after the insertion the cutting wire was extruded and rotated to cut out a core of tissue.
 Transorbital lobotomydeveloped in italy, popularized in the US by Walter Freeman.  Inserting an ice-pick-like device under the eyelid and driving it through the orbital with a mallet, where it is waved back and forth, severing the connection between prefrontal lobes and the rest of the brain.
 Psychosurgery

any brain surgery that is meant for the treatment of a psychological problem

 Dualism(Aristotle)

the mind and the body are separate entities

 Interactionism

(Cartesian Dualism) the mind and the body are separate, but they   interact in some way.

 Epiphenomenalism(Aristotle)the mind and consciousness are incidental bi-products of a functioning human brain.
 Monoismthe mind and the body are one and the same - and the brain is really all there is, the mind is an illusion.
 Functionalism

The mind is what matters, no matter what produces it, whether that be a  coke machine or brain per say. 

  The machine should be a “black box”.

 Philosophical Assumptions neuroscientists make

1.                           Materialism

2.                           Determinism

3.                           Mechanism

4.                           Reductionism

5.                           Emergent Properties

 Materialism

Anything other than matter and energy is outside the realm of physics and therefore outside the realm of science generally (including neuroscience)

 DeterminismEvery even has a cause.
 These causes can be determined, discovered, cataloged, and used to predict future events.
If events were not determined, then science would be a poor career choice because there would be no certainty. FUNDAMENTAL to science.
 Distal causation

distant, remote, complex to understand

 Proximal causationimmediate causes: Stimuli and environment.
 MechanismCauses have a Physical basis. 
Only physical determinants of behavior can be quantified, observed, and measured. 
The universe behaves in a regular and orderly manner - stuff doesn’t just happen.
 Ultimate causationTeleology
-  Why does this happen?
-  Neuroscience can only answer some of these ?’s
-  Why are we here?
-  We cannot answer why because science is not adept at answering teleology questions.

 ReductionismComplex phenomena can often be “reduced” to simpler physical  processes.  
Each finer level of analysis relies on more basic, fundamental, more molecular processes.  
Explanations tend to move from the molar(behavioral) to the molecular (anatomy, physiology, neurochemistry).
 EmpiricismA method of obtaining information by observation and experimentation(data).
These data are used to generate explanations, hypotheses, and theories. The hypotheses and theories are then tested.
Predictive theories are retained, faulty ones are modified or discarded.
Scientists replicate the work of others and either verify it or criticize it. - Theories are then corrected.  Science self corrects.
 Natural HistoryUnderstanding the earth, and the history of life on earth, from a      scientific perspective
 CosmologyTheories of the origin of the earth, of life, of the universe.
 EvolutionThe theory of evolution is a comprehensive, integrative, scientific account of  the origin of species
 Genetics

The biological mechanisms that code for an organisms structure and  function, including reproduction.

Other theories of evolution had been proposed earlier, but Darwin’s was novel because of the mechanism: Natural Selection

 Neo-Darwinian TheoryBasic ideas of Darwinian Evolution intact.
Incorporates modification based on recent evidence(eg. Gould’s notion of “punctuated equilibrium”).
Incorporates modern genetic theory, Mendel’s work was done more than 30 years after “Origin of Species”, well after Darwin’s death). 
Modern research is biochemical genetics
 Divisions of Neo-Darwinian Theory of Evolution

1.  Environment

2.  Life

3.  Heredity

4.  Continuity

5.  Sex

6.  Variability

7.  Natural Selection

 Neo-Darwin Evolu: Environmentlife exists in an uncaring environment.
Environment provides ecological niche
 Neo-Darwin Evolu.: Life

Some groups of chemicals have the ability to self replicate.

On earth, these chemicals are DNA.

With unlimited resources, life replicated unchecked.

 Neo-Darwin Evolu.: HeredityCharacteristics are passed from parent to off-spring.DNA codes for these characteristics, and is passed from parents to off-spring at conception.
 Neo-Darwin Evolu.: Continuity

Organisms related not only to parents, but to every other living organism.

 Notion of “Common Ancestor”. 

  Some organisms have recent common ancestors(humans and monkeys), others more remote(humans and armadillos).

  Doesn’t mean one organism “evolved from” another.

 Neo-Darwin Evolu.: SexGenes perpetuate themselves through sexual reproduction.  Not all members of a species reproduce with the same success (or with the same frequency). 
Most organisms reproduce in ever-increasing numbers.
 Neo-Darwin Evolu.: Variability

Both parents contribute equally to genetic makeup of off-spring.  However, the genetic “mixture” is different each time (that is, the 50% from father is randomly determined for each organism)  

Some errors get  introduced during reproductions (eg. Genetic mutations). 

 Some combinations of genes are more successful than others.  Some isolated populations change enough over time that they cannot interbreed: Speciation

 Neo-Darwin Evolu.: Natural SelectionUsually, resources are limited: Selectivepressure
 Organisms must compete for limited resources.  
Some members of a species are better able to compete: Survival of the fittest.
 FitnessFitness is defined as an organism’s ability to survive and reproduce.  
“Success” is the organism’s ability to pass on its genes to future generations.
Some members of a species are better able to compete: survival of the fittest. 
Richard Dawkins’ The Selfish Gene--the idea of inclusive fitness.  
Fitness only has meaning in the context of specific selective pressures(environments), as an environment changes, so does fitness.  
Fitness doesn’t mean better, just better adapted to the environment, and evolution doesn’t mean progress or           improvement, it only means that a species has changed in response to changes in the environment.
It is meaningless to speak of organisms being “more highly evolved”. 
 Reasons why Darwinian Evolution is so controversial

1.  Places humans squarely within the realm of all organisms, not “above” the collection

2.  Removes humans from being a “special” creature (humans can still be unique)

3.  Often misunderstood as an attack on religious explanations, or as being incompatible with theology or religion -- not true

4.  Fails to address the ultimate “why” question -- our purpose for being(all scientific theories fail at this)

 Behavioral Genetics

A technique for assessing the relative contribution of genetic and   environmental factors in behavior.

 Assumes behavior has causes that can be grouped into 2 broad categories:
 behavioral genetics assumes behavior has causes that can be grouped into 2 broad categories:

1.    Genetic Factors: Not “a gene” but all the genetic factor which contribute to the behavior in question.

2.     Environmental Factors: Everything that one experiences in one’s life.

 Genetic Factors

The total contribution of genetic factors to the specific behavior is question is expressed by a single number called a heritability coefficient (h^2)

 HeritabilityThe proportion of variability in a given population which can be attributed to genetic factors.
 Environmental Factors

Shared Environmental Influence (Es) - influences shared by all members of a family


Unique Environmental Influence (ENS) - All other enviro influences

 Main problem in assessing the contribution of genetic and environmental influencesMost individuals who are related genetically also share environmental  background. 
One needs to find individual who share genetic influences,environmental influences, both and neither, and compare their behavior.
 3 major conclusions about Behavioral Genetics

1.  The degree of Genetic Influences typically ranges between .4 and .7, roughly half of the variability can be attributed to genetic factors

2.  Effects of the Family Environment is minimal Es<.1, usually close to 0

3.  A significant proportion of behavior can be attributed neither to genetic factors nor the family, and is presumably caused by unique environmental factors. (Ens ~ .5)  Friends may be the most important environmental influence.

 Heritability FormulaVB = h2 + (ES + EU) + h2 x E(S+U) + ε
 Behavioral Variance (=) is composed ofgenetic, environmental, and g X e influences, plus some Error -- because we don’t make perfect predictions.
 Central Nervous System(CNS)Involves the brain and the spinal cord.
 Peripheral Nervous System (PNS)Located outside of the skull and spine.
Serves to bring information into the CNS and carry signals out of the CNS. 
The two PNSs include: Somatic Nervous system (afferent(sensory) and efferent nerves(motor), sensory and motor respectively) and Autonomic Nervous System (efferent, sympathetic and parasympathetic nerves)
 Autonomic Nervous SystemAll nerves are efferent(info.out).  
Sympathetic and parasympathetic nerves generally have opposite effects. 
2 stage neural paths, neuron exiting the CNS(presynaptic) synapses on a second stage neuron, in a ganglion, before ending on the target organ(postsynaptic).
 Sympathetic nerves

located in the Thoracic and lumbar regions of the spine. 

  Control your “fight or flight” response.  

They are second stage neurons, ganglia, are far  from the target organ.

 Parasympathetic nerveslocated in the Cranial and sacral regions of the spine.  
Meant to “Rest and restore”(returns body to normal after being altered by sympathetic stimulation. 
Second stage, ganglion, located near the target organ.
 Autonomic Nervous System Controls

Heart (SNS up; PNS down); 

BP (SNS up; PNS down); 

Cortisol levels (SNS up);

 Pupil size;

 Blood flow to sex organs and orgasm;

 Blood to gut (SNS up; PNS down);

 Sweating (SNS up); 

Micturition(need both SNS and PNS); 

Glycogen Release (SNS up)

 3 meninges covering the CNS in bone

1.  Dura mater - tough outer membrane

2.  Arachnoid membrane - web-like

3.  Pia mater - adheres to CNS surface

 Cerebrospinal fluid (CSF)fluid that serves as a cushion; also has ionic function and     acts like plasma
 Ways you protect your brain

Chemical protection - The Blood-Brain Barrier

 Physical protection - Skull; Meninges; Cerebrospinal fluid.

 : Blood-Brain Barrier

unfenestrated endothelial cells of capillary walls prevent entry of     many larger, non-fat soluble molecules - unlike outside the brain.

 Golgi Stainallows for visualization of individual neurons (light microscope)
 Nissl stain

selectively stains cell bodies (light microscope)

 Electron microscopy

provides information about the details of neural structure - uranyl & osmium stains (heavy metals: electron beam dense)

 Areas of the Spinal Cord

Gray matter(inner component, primarily cell bodies)

 White matter(outer area, mainly myelinated axons)

 Dorsal(afferent, sensory)

 Ventral(efferent, motor).

  forebrain

midbrain

hindbrain

spinal cord

  telecephalon (cerebral hemispheres)

diencephalon

mesencephalon (midbrain)

metencephalon

myelencephalon (medulla)

spinal cord
 Myelencephalon

Medulla

Composed largely of tracts

 Origin of the reticular formation

 MetencephalonMany tracts
 Pons(ventral surface)
Cerebellum(coordination)
  1. pons

2. reticular formatoin

3. medulla

4. cerebellum
 MesencephalonMidbrain
Tectum(superior colliculi, inferior colliculi)     Tegmentum(Reticular formation, Cerebral aqueduct, Periaqueductal gray, substantia nigra, Red Nucleus)
  1.  superior colliculus
2.  periaqueductal gray
3.  mesencephalic reticular formation
4.  cerebral aqueduct
5.  red nucleus
6.  substantia nigra
7.  tectum
8.  tegmentum
 Diencephalon

Thalamus(Massa intermedia, lateral geniculate nuclei, medial geniculate nuclei, ventral posterior nuclei)

Hypothalamus(mammillary bodies)

 Optic chiasm

Pituitary gland.

 TelencephalonCerebral Cortex
Convolutions serve to increase surface area
 Longitudal fissure - a groove that separates right and left hemispheres
Corpus callosum - largest hemisphere-connecting tract
 4 lobes of the Cerebral Cortex

1.  Frontal (Future planning, speech production, behavior inhibition

2.  Occipital (vision)

3.  Parietal (touch, cross-modal matching, language, spatial skills

4.  Temporal (Language reception, hearing)

 Limbic System

Subcortical structure

 Telencephalon

 Regulation of motivated behaviors

  Includes: Mammillary bodies, hippocampus, amygdala, fornix,             cingulate, septum.

 Basal ganglia motor systemSubcortical structure
 Facilitate movement &/or suppress movement
Includes: Amygdala, striatum (caudate nucleus+putamen), globus  pallidus.
 Contrast X-raysinject something that absorbs X-rays less or more than surrounding tissue, such as cerebral angiography
 X-ray computed tomography (CAT or CT)

Computer-assisted X-ray procedure

 Provides 3-D representation of the brain

The brain is viewed in slices

 Good  resolution(anatomy only)

 Shows pathology, bleeds, deformity very well

 Resolution: couple of mm.

 Magnetic Resonance imaging (MRI)

High resolution images

 Constructed from measurements of waves that hydrogen atoms emit when activated within a magnetic field
High field strength magnet - cooled by liquid gas

 Cylinder, noise, constraint stress

 Very precise view of normal and abnormal brain
 Can also be used to study metabolism.

 Positron emission tomography (PET)

Provides images of brain activity

Scan is an image of levels of radioactivity in various parts of one horizontal level of the brain

A radiolabeled substance is administered by injection prior to the scan

 As the iostope decays the PET detects the decay and plots anatomy and metabolism.

 Functional MRI (fMRI)

Provides images of brain structure and activity

 As with MRI uses strong magnetic field

 Structure is imaged using waves emitted by hydrogen ions acting in an intense magnetic field

Function is imaged using signal created from interaction between oxygen and iron in the blood

 Fast but not as fast as we would like(on the order of seconds)

 Magnetoencephalography (MEG)A measure of neural activity
 Measures changes in magnetic fields on the surface of the scalp(created by underlying patterns of neural activity)
 Fast temporal resolution - sub-seconds resolution.
 Transcranial magnetic stimulation (TMS)

NOT a measure of neural activity, but  provides an experimental probe to alter neural activity

TMS applies a brief, strong magnetic field that alters neural activity(can either activate or deactivate brain structures, observe changes in behavior, or create “reversible Lesions” which mimic lesions.

 - Scalp electroencephalography (EEG)measure of gross elecrtical activity of the brain
 uses electrodes attached to the scalp
 Wave for assessment(records brainwaves, and when your brainwaves cooperate then you are rewarded with a positive   feedback loop.  Brain is gently nudged into behaving in a new way).
 Electromyography (EMG)

the technique of measuring the voltage generated by muscle           activity

 Indicates tension of muscles(level of contraction)

 Measures of electrodermal activitySkin conductance level (SCL):measure of the background level of skin conductance that is associated with a particular situation
Skin conductance response(SCR): measure of the transient changes in skin conductance that are associated with discrete experiences.  Skin conductance from emotional arousal.
 Electrocardiogram (ECG or EKG)

 Measures cardiovascular activity such as heart rate,   blood pressure, and blood volume

 Often used to link physiological changes with emotional state - level of arousal.

 

 Stereotaxic surgery

requires use of stereotaxic atlas to locate brain structures like a        road map, and a stereotaxic instrument

 - two part tool:

1. a head holder, which firmly holds the patients brain in the correct position and orientation

2. and an electrode holder, which hold the device to be inserted.

 Aspiration lesionsused when a lesion is to be made in an area of cortical tissue that is accessible to the eyes and instruments
Cortical tissue is suctioned off through a finetipped handheld glass pipette
Because Underlying white matter is slightly more resistant to suction, a surgeon can delicately peel off the layers of cortical tissue from the surface, leaving the underlying white matter and major blood vessels undamaged
 Lesion methodsBilateral and unilateral lesions
Several procedures each require careful interpretation of effects.
1.  aspiration lesions
2.  radio-frequency lesions
3.  knife cuts
4.  cryogenic blockade
 Radio-frequency lesionsSmall subcortical lesions made by passing radio-frequency current through the target tissue from the tip of a stereotaxically positioned electrode
 Knife cutsCutting is used to eleminate conduction in a nerve or tract
 . Cryogenic blockadeusing an implanted cryoprobe with flowing coolant fluid to cool the neurons to the point of not firing
 Electrical stimulationLesioning can be used to remove, damage, or inactivate a     structure.
Electrical stimulation may be used to “activate” a structure.  Application of drugs to brain sites-stimulate and inhibit.  Stimulation of a structure may have an effect opposite to that seen when the structure is lesioned.
 Invasive electrophysiological recording methods1.  Intracellular unit recording

2.  Extracellular unit recording

3.  Multiple-unit recording

4.  Invasive EEG recording
 Intracellular unit recordingmoment by moment record of the graded fluctuations of one neurons membrane potential.
 Extracellular unit recordinga record of the firing of a neuron but no info on the membrane potential, electrode is placed beside a neuron so that when the neuron fires, an electrical disturbance
 Multiple-unit recordingThe electrode tip is larger than the microelectrode used in extracellular unit recording, allowing it to pick up signals from many neurons and slight shifts in its position due to movement have little effect on the overall signal. 
Produces a graph of the total number of recorded action potentials per unit of time
 . Invasive EEG recording

EEG signals are recorded through a large implanted electrodes rather than on the scalp

Cortical EEG signals are frequently recorded through stainless steel skull screws, whereas subcortical EEG signals are recorded through stereotaxically implanted wire electrodes.

 Routes of drug administration1. Fed to the subject
 2. injected through a tube into the stomach(intragastrically); or 3. injected hypodermically into the peritoneal cavity of the abdomen, into a large muscle, into fatty tissue beneath the skin, or into a large surface vein. 
For drugs that do not readily pass the blood-brain-barrier, a fine, hollow tube known as a cannula is stereotaxically inserted into the brain
 Selective chemical lesions

Make a more selective lesion by injecting neurotoxins that have an affinity for certain components of the nervous system.  

 2-Deoxyglucose Technique of measuring chemical activity of the brain

Inject animal with radioactive 2-DG and allow it to engage in behavior of interest

 The subject is killed and brain slices are subject to autoradiography; coated with photographic emulsion, stored in the dark, and developed like film.

The areas of the brain that absorbed high levels of 2-DG during the test appear as black spots on the slides.  

The density of the spots are then color coated.

 Cerebral Dialysismeasures extracellular concentration of specific chemicals in live animals.
Implant a fine tube with a short semipermeable section, this section is positioned in the brain structure of interest so that the extracellular chemicals diffuse into the tube.
The chemicals are then frozen for later testing or directly put in a chromatograph
 Locating Neurotransmitters and receptors in the brainDye or radioactive labels used to visualize the protein of interest. 
1.  Immunocytochemistry 

2. In situ hybridization


 
 Immunocytochemistry

labeling certian neuroproteins’ antibodies with a dye or radioactive element and then exposing slices of brain tissue to the labeled antibodies

 Regions of dye accumulation in the brain mark the locations of the target neuroprotein

 In situ hybridization

first obtain hybrid RNA that has a base sequence complementary to that of the mRNA of the target protein.

The hybrid RNA are labeled with dye or radioactive element.

Brain slices are then exposed to the labeled RNA, they bind to the mRNA, thus marking the location of neurons that release the target.

 Gene knockout techniquescreating organisms that lack a gene. 
Subjects missing a given gene can provide insight into what the gene controls.
Knockout mice. 
The results are difficult to interpret since most behavior is controlled by many genes and removing one gene may alter the expression of others, including compensation for the missing gene.
Antisense drugs block expression of a gene.
 Gene replacement techniquesPathological genes from human cells can be inserted into mice.  Mice that contain genetic material of another specie are called transgenic mice.  
 Behavioral paradigm

A single set of procedures developed for the investigation of a         particular behavioral phenomenon.

 Humans in Natural experiments

Time consuming: only conducted on a small portion of  those with brain damage.

Assists in diagnosing neural disorders.

Serves as a  basis for counseling/caring for patients.  Provides information on effectiveness and side effects of treatment.  

 Single-test approach to neuropsychological testingUsed to differentiate brain damage from functional (psychological) cause. 
 Standarized-Test-Battery approach to neuropsychological testing

Same goal as single test approach, but involved sets of tests rather than a single test.

 Halstead-Reitan: preformed poorly by brain damaged patients.

 Customized-Test-Battery approach to neuropsychological testing

Predominant approach

 Subjects given a common battery of test and depending on the general diagnosis(such as memory problem) a customized 2nd set of test would be given to assess the specifics.

 Tests of the common neuropsychological test battery1.  intelligence

2.  memory

3.  language tests

4.  language laterlization
 Intelligence test of the common neuropsychological test batteryWechsler Adult Intelligence Scale
WAIR, an IQ test
 Memory test of the common neuropsychological test battery
digit span subtest - ids the longest sequence of random digits that a patient can repeat correctly. 
 Language test of the common neuropsychological test batteryto find problems of phonology, syntax, semantics
 Language laterlization test of the common neuropsychological test batteryused to ID language-dominant hemisphere
Sodium amytal anesthetizes one hemisphere
Dichotic listening - ear contralateral to dominant hemisphere shows superior hearing ability
 Tests of specific neuropsychological function1.  Memory

2.  Language

3.  Frontal-Lobe Function
 Memory tests of specific neuropsychological function
Repetition Priming Test
4 questions must be answered following a positive on the memory section of the common test battery
1.  short-term, long-term, or both?
2.  Anterograde or retrograde?
3.  Semantic(knowledge of the world) or episodic(personal experience)?
4.  Explicit(memories in which the patient is aware and can express verbally) or implicit(improved performance of the patient w/o the patient being conscious of them)? 

 Repetition Priming Test
Shown a list of words, then at a later time they are asked to complete word fragments, many of which are from the initial list.
 
 Language tests of specific neuropsychological functionproblems of phonology, syntax, or semantics
 Frontal-Lobe Function tests of specific neuropsychological functionWisconsin Card Sorting Task - each card has one, two, three, or four identical symbols; patients are given 4 unique cards; the patients are asked to sort a deck without knowing the sorting order, once a card is placed, the tester gives a yes or no, once the patient learns the pattern they shift the required sorting order
Frontal lobe damage causes the continued sorting principle for 100 or more trials after it has become incorrect
 Assumptions of cognitive neuroscience1.  Each complex cognitive process results from the combined activity of simple cognitive processes(constituent cognitive processes)

2.  Each complex cognitive process is mediated by neural activity in a particular area of the brain(specificity of effect.) But, all areas are connected and damage in one can affect others(global effects)

 Main goal of cognitive neuroscience

To identify the parts of the brain that mediate various constituent cognitive processes.

 

 Paired-image subtraction technique

Compare PET or fMRI images during several different cognitive tasks, you look for areas that are different with different tasks.

 

 Biopsychological Paradigms of Animal BehaviorProcedures developed for the investigation of a particular behavioral phenomenon
Assess behavioral function on common problem-focused behaviors in humans and non-humans
 Paradigms for assessment of species-common behaviors (4 tests)Behaviors that are displayed by virtually all members of a species, or at least by all those of the same age and sex.
1.  open field test
2. Tests of aggressive and defensive behavior
3.  Tests of Sexual behavior 
4.  Tests of behavioral inhibition
 
 Open-Field test

a subject is placed in a large, barren chamber, an its activity is recorded.

Low activity and high poop count is frequently used as an indicator of fear

Fearful rats are highly thigmotaxic(rarely venture away from the walls of the test chamber and rarely engage in activities such as rearing and grooming)

 

 Tests of Aggressive and defensive behavior

Aggression and defensive behavior can be observed and measured during combative encounters between the dominate male and a smaller male intruder. <----- Colony-intruder paradigm.  

Piloerection, lateral approach, and flank and back biting indicate aggression

freezing, boxing, and rolling over indicate defensive

Elevated plus maze(4 armed plus shape, 2 sides have walls, 2 don’t) commonly used to study anxiolytic drugs.

 Tests of sexual behavior in animal behavior

Intromission(8===D <>). 

Measure the number of mounts required to achieve intromission, the number of intromissions required to achieve ejaculation, and the interval between ejaculation and the reinitiating of mounting. 

 Traditional Conditioning Paradigms1. Pavlovian conditioning
2. Operant conditioning
 1. Pavlovian conditioningpairing an unconditioned stimulus with a conditioned stimulus, e.g. Pavlov’s dogs
 Operant conditioningreinforcement and punishment
e.g. self-stimulation paradigm<animal presses lever to deliver stimulation to the pleasure centers of the brain>
 Conditioned Taste AversionPairing something that makes an animal ill(emetic) with a taste, challenged existing assumptions about conditioning(not always a gradual process, showed that temporal contiguity is not essential for conditioning<rats became averted by the taste even if illness hasn’t occured yet>, and finally it challenged the view that conditioning proceeds in basically the same manner regardless of the particular stimuli and responses under investigation) , animals appear prepared to associate tastes and illness
 Radial Arm MazeSpatial learning
 Morris Water MazeSpatial learning
rat must find platform in an opaque pool
Complex cognitive task preformed under sever stress
Patton & Stanford: effects of Prozac on fetal development.
 Green Florescent Protein (GFP)

Exhibits bright green fluorescence when exposed to blue light. Variants of the gene for GFP can express other colors. 

These GFP genes can be inserted into DNA of neurons - color can then be viewed when targeted neuronal genes are expressed giving us a BRAINBOW!!!

 Antidromic conductionIf electrical stimulation of sufficient intensity is applied to the terminal end of of an axon, an action potential will be generated and will travel along the axon back to the cell body.
 Orthodromic conductionnatural direction of Action potentials
 nodes of Ranvier

The gaps between adjacent myelin segments

 ions can only pass here on the axon.

 

 Saltatory conductiontransmition of action potentials in myelinated axons.
 the AP jumps along the axon from node to node
 Directed synapsessynapses at which the site of neurotransmitter release and the site of neurotransmitter reception is in close proximity.  
 Nondirected synapses synapses at which the site of release is at some distance from the site of reception.  
 Neuropeptide

short amino acid chains comprising of 3-36 amino acids


 short proteins.

 

 (Fill in the blank) cytoplasm, synaptic vesicles, Golgi complexSmall molecule neurotransmitters are typically synthesized in the __________ of the terminal button and packaged in _____________ by the buttons _________.
 Coexistencemany neurotransmitters contain 2 NTs
 ExocytosisNT release
 ligandany molecule that binds to another
 Autoreceptors 
 Acetylcholinesteraseenzyme that breaks down acetylcholine
 Gap junctionsnarrow spaces between neurons that are bridged by fine tubular channels, called connexins, that contain cytoplasm
 Amino Acid NTs

Glutamate, aspartate, glycine, gama-aminobutyric acid (GABA)

 

 Glutamate

most prevalent excitatory NT in the mammalian central nervous system

 

 Monoamine NTs

slightly larger than amino acid NTs and their effects tend to be more diffuse, also released diffusely.  Dopamine, epinephrine, norepinephrine, and serotonin.

 

 2 groups of MAONT

Catecholamines (Dopamine, norepinephrine, epinephrine) Synthesized from l-dopa, Indolamines(serotonin, synthesized from tryptophan)

 Acetylcholine

small molecule NT at neuromuscular junctions, at many of the synapses in the ANS, and at synapses in several parts of the CNS.  Released by cholinergic neurons.

 Soluble-gas NTs

Nitric Oxide and carbon monoxide.

Produced in cytoplasm, diffuse out of neuron into extracellular fluid and then into nearby cells.

Stimulate a second messenger.  Last a few seconds. 

 Involved in retrograde transmission(send signals from post to presynapses)

 Endocannabinoids

Nts that are similar to THC.

Anandamide.

released from dendrites and cell body, effect presynaptic neurons, inhibit these neurons synaptic transmission.

 Neuropeptide transmitters

Pituitary peptides(hormones released by pituitary), hypothalamic peptides, brain-gut peptides, opioid peptide, miscellaneous peptides.

 Agonistfacilitate the effects of a particular NT
 Antagonists

drugs that inhibit the effects of a particular NT. 

Receptor blocker

 Enkephalinsendorphin from opioid
 Oral ingestion of drugs influenced by digestive system, small molecules act more rapidly, unpredictable
 Inhalation

more direct route, rapid effects.

difficult to regulate a dose.

 

 Mucous membranes

nose, mouth, rectum.

 very rapid

 Injection subcutaneous, intramuscular, intravenous.
 fast and direct.
 Metabolic tolerancea decrease in the amount of drug due to metabolism
 Functional tolerance a decrease in drug effect because of changes in receptor sensitivity
 Contingent tolerancedemonstrations that tolerance develops only to a drug effects that are actually experienced.
 Situational specificity (conditioned drug tolerance)

tolerance effects are maximally expressed only when a drug is administered in the same situation in which it has been previously administered

 Tobacco2nd most widely used psychoactive drug behind caffeine.  Nicotine is the major ingredient.
Contains 4000 different compounds with approx. 1500 coming from additives, pesticides and other organic/metallic compounds.
Compounds include CO, ammonia, hydrogen cyanide, nitrites, and radioactive compounds.
 43 known or suspected carcinogens are found in cigarette smoke.
 Nicotine

Lethal dose of nicotine is 60mg.

 Typical cig will deliver .05-2.5mg.

 Reaches the brain quickly and facilitates the release of dopamine in the nucleus accumbens(group of cell bodies in the ventral striatum<major target of the dopamine system>).  

Buerger’s disease. 

Consequences of long term use include an increase risk of: cancer, emphysema, and respiratory infections.

 Alcohol

Depressant, exact neural mechanism unknown, acts on GABA, glutamate, dopamine, and serotonin systems. 

 Results of chronic use: blackouts, reduced brain activity in parietal and frontal regions, and Korsakoff’s syndrome.

 Marijuana

cannabis sativa, wild cannabis not very potent, historically used as an analgesic, hypnotic, and anticonvulsant, THC acts at the cannabinoid receptor, anandamide seems to be an endogenous cannabinoid.  

May play a role in pain and memory.

 Opiatesopium is found in the opium poppy, the most notable psychoactive ingredient is morphine, Opiates mediate pain perception, anxety, sedation and pleasure, 
Euphoria mediated by opioid auction on the VTA.
 Intracaranial self-stimulation (ICSS)

Discovered in the 1950s by james olds and peter milner.

brief bursts of weak electrical stimulation to specific pleasure centers.

  These centers of pleasure also mediate the pleasurable effects from eating, drinking, and sex. 

  Similar to lever pressing for rewards. 

 

 Mesotelencephalic Dopamine System

dopaminergic neurons the project from the midbrain to the telncephalon. 

  Agonists increase while antagonists decrease dopamine. 

  Damage to MDS structures disrupts ICSS.

 Dopamine and Human Addicts Imaging studies show involvement of dopamine in addiction. 
Dopamine activity is muted in drug addict individuals. 
 In the presence of drug stimulation, the mesotelencephalic dopamine system became hyperactive.
 Epilepsy

Description: Intermittent disruption of brain function produced by a sudden, intense, uncontrolled discharge of neurons. 


  Cause:  Varied: Congenital, stroke, tumors, trauma, poisioning. 

  For all types of epilepsy, the concordance rate is .44 for monozygotes and .10 for dizygotes.  


Treatment: surgery, pharmaceutical interventions.

 

 Generalized seizuresno localized onset, bilateral symmetry, most common generalized seizures are termed grand mal and petit mal.
Petit mal seizures are characterized by a 3-per-second-spike and wave discharge.
 Partial SeizuresHave a clear point of origin.
 Asymmetrical.
 Divided into simple and complex.
 simple partial seizures have motor and/or sensory symptoms (jacksonian march).
complex partial seizures have psychological symptoms and may develop into a psychomotor attack.
 Parkinson’s DiseaseMovement disorder characterized by: tremors and stiffness; tremors are pronounced during inactivity; muscle rigity; difficulty initiating movement; slowness of movement; mask-like face...
 

 Cause of Parkinson's Disease No single cause; Infections, strokes, tumors, neurotoxic events, trauma, and genes have all been implicated, associated with loss of dopamine neurons in substantia nigra.  Early onset PD has a stronger genetic component than late, concordance rates among twins are relatively low, chromosome 4 has been implicated, obviously, there is a strong environmental component.
 Treatment for Parkinson's DiseaseTreatment: Pills, Surgical lesions, deep brain stimulation.
 Cause of Huntingtons DiseaseDominant Huntington gene that produces the huntington protene, if you have it you will get it, 50% chance of passing it on. 
 Huntingtons DiseaseProgressive terminal disorder of motor and intellectual function.
Characterized by: chorea(difficulty speaking), difficulty swallowing, personality changes and withdrawal from social activities, paranoia, hallucinations, psychosis, depression, memory loss, poor decision making.
 Treatment for Huntingtons Disease

NONE!

 Multiple SclerosisA progressive disease of the CNS myelin.  
Symptoms: dizziness and loss of balance, fatigue, hand or leg weakness, inflammation of nerves in the eye, localized tingling or numbness, visual impairments, including blurred or double vision.
 Cause of Multiple SclerosisEnvironmental, Genetic(monozygotes 30% vs 5% for dizygotes), Autoimmune response, viral trigger
 Treatment for Multiple Sclerosis

No cure, Pills, Rehab.

 

 Alzheimer’s Disease 
 Cause of Alzheimer’s DiseaseMost common cause of dementia, likelihood of developing it increases with age.
Progressive, with early stages characterized by confusion and a selective decline in memory. 
Must observe neurofibrillary tangles and amyloid plaques to be sure it was Alzheimer’s.  
Several genes ID’d as involved w/ early onset AD.
All affected genes are involved in synthesis of amyloid or tau, a protein found in the tangles.  Not clear what comes first- plaques or tangles. 
Decline in acetylcholine levels.
 Kindling model of epilepsy

A series of periodic brain stimulations eventually elicts convulsions - the kindling phenomenon (Neural changes are permanent).  Convulsions are similar to those seen in some forms of human epilepsy - but they only occur spontaneously if kindled for a very long time.  

Comparable to the development fo epilepsy seen following a head injury

 MPTP model of Parkinson’s

 Synthetic heroin produced symptoms of PD, contained MPTP(causes cell loss in the substantia nigra, like that seen in PD).  Deprenyl can slow the progression of PD.

 Anterograde Neuron regeneration

Between cut and synaptic terminal.

Cut off from metabolic center, swells and breaks off within a few days

 Retrograde Neuron degenerationCut and cell body
Progresses slowly, may survive if regenerating axon makes new synaptic contact
 Neural regenerationdoesn’t occur successfully in mammals and other higher vertebrates.
capacity for accurate axonal growth is lost in maturity.  Virtually nonexsistent in the CNS and unlikely, but possible, in the PNS
 Schwann cellspromote neural regeneration.
 neurotropic, CAM’s provide a pathway.
 Oligodendrogliaactively block regeneration
 Cognitive reserve

education and intelligence - thought to play an important role in recovery of function - may permit cognitive tasks to be acomplished in new ways.

 

 How to reduce brain damage by blocking neurodegeneration

Apoptosis inhibitor protein.

 Nerve growth factor(blocks degenerationon damaged neurons).

Estrogens - limit or delay neuron death

 Promoting regenerationCNS neurons can be induced to regenerate.
Eliminate inhibition of oligodendroglia and provide schwann cells.
 Promoting recovery by neurotransplantation

Fetal tissue(fetal substantia nigra cells used to treat MPTP-treated monkeys, treatment was successful, limited success in humans)


 Stem cells(rats w/ spinal damage “cured”, but much more research is needed.)

 

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