Neurobiological Basis of Human Behavior

8/12/2019 Neurobiological Basis of Human Behavior

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There is nothing in our minds thatdoes not go through the senses


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Objectives

To discuss the neuroanatomicalstructural and functionalorganizations of the brain system

To understand the molecular andneurobiological basis of behavior.


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Organization of the Nervous System


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INTRODUCTORY CONCEPTS

Sensory receptors areTRANSDUCERS

ONTOGENY RECAPITULATESPHYLOGENY

HIGHER CENTERS INHIBIT LOWERCENTERS


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Ventral tegmental

area

Locus

ceruleus cerebellum

Inferior

colliculus

Superior

colliculus

Periaqueductal

gray area

Hippocampus

Arcuate

nucleusAmygdala

Nucleus

accumbens

Prefrontal

cortex

The Mesolimbic System

(James Papez, 1937)


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Key words:

EXCITABILITYATION

COMMUNICATION


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Limbic

system


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Anatomy of Neuron:

Dendrites: take inputinformation into neuron

Cell body: cellular metabolism,incoming signal communicated

Axon: carriesinformation away from cell

bodies towards output terminals


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12/72Illustration by Lydia Kibiuk

The Action Potential

Resting membrane

potential: -70 mV

Depolarization

Nerve Impulse

Synaptic Transmission


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hyperpolarization

The Action Potential


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Levels of Neuroanatomical study

Histology

Cytoarchitecture

Behavioral Neuroanatomy Sensory systems

Motor systems

Associated Units


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Histology

Neurons

Glial cells


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Neurons

Polarized,elongated cellscapable of

instantaneously,intracellularcommunication

Transmission of

information

Cell body

axon

nucleus

dendrites

synaptic cleft


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Receptors activate orinactivate ion channelswithin the membraneand regulate the voltage

potential across themembrane

passage of Ca+ altersthe ionconcentrations andactivates the 2ndmessenger cascade

transmitter

gate

pore

channel

transmitter

transmitter


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The Simple Synapse

Synapse

Neutrotransmission

Pre-synaptic Post-synaptic


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The Synapse


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The Synapse


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Pre-synaptic

Neuron

Post-synaptic

Neuron

TransmissionCa++

reuptake

Synaptic vesicle

Synapse

Action Potential

1.

2.

3.

4.

5.

6.

XNa+

K+

7.

Process of Synaptic Transmission

Na+

K+

Neurotransmitter

release


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= receptor

= enzyme

cell body

receptors beingtransported

axon terminal

receptors being inserted

into membrane

1-8Stahl S M, Essential

Psycho pharmacolog y (2000)

Axonal transport of presynaptic receptor


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Action potential

instantaneous pulses of membranedepolarization

myelin sheath - increase the rate of AP alongthe axon

Synaptic cleft - AP triggers the release ofchemical neurotransmitters, which enter thesynaptic cleft and bind to receptors

Neuronal cell bodies - gray matter Myelinated axon tracts - white matter


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Glial cells - regulate the extracellular environment

astrocytes - ensure synaptic communicationand regulate extracellular ion concentrations

oligodendrocytes - serves to insulate fibers inthe fiber tracts

microglia - immune system cells

Cytoarchitecture

relfers to the local organization of neurons

47 areas - columnar organizations - acquirespecific functions


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Nervous system: sensory, motor

and association

Sensory systems

processes external stimuli into neuronal impulses andcreate an internal representation of the external world

Motor systems enable people to manipulate the environment and to

influence others behavior through communication

Associated units -

where the sensory inputs, representing the external

world, is integrated with internal drives and emotionalstimuli and in turn drive the actions of the motor units


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THE BASIC UNIT OF BEHAVIOR IS

THE REFLEX ARC.

RECEPTOR

SENSORY/AFFERENT NEURON

SYNAPSE IN THE CNS MOTOR/AFFERENT NEURON

EFFECTOR


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Sensory systems

transforms external stimuli into neuralimpulses and then filter out irrelevantformation to create an internal image of

the environment which serve as the basisfor reasoned thought.


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Sensory systems

Sensory inputs

Auditory

Gustatory

Visual Olfactory

Tactile

Alteration of conscious perception throughhypnosis

Hypnosis - state of heightened suggestibility -gross distortions of perception of any sensorymodality

Depend on the persons goals and emotional

state


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Motor systems

Brainstem

Corticospinal tract

Basal ganglia

Corpus striatum - caudate and putamen Globus pallidus

Substantia nigra

Subthalamic nuclei

Cerebellum Motor cortex

Autonomic cortex


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Brainstem

primitive systems produce gross coordinatedmovements of the entire body

Corticospinal tract

controls fine movements and dominates thebrainstem

Motor strip - posterior frontal lobe

planned movements

Basal ganglia subcorticate matter that medicate postural tone

Four distinct ganglia: striatum, pallidum, substantianigra, subthalamic nuclei


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Corpus striatum - caudate and putamen

harbor components of both motor and associatedsystems

plays an important role in the modulation of motor

acts

decreased activate is related with OCD behavior

when functioning properly, acts as the gate keeperto allow the motor system to perform only thoseacts which are goal directed.

Overactivity of the striatum - due to lack ofdopaminergic inhibition - results in bradykinesia -an inability to initiate movements


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Globus pallidus

receives inputs from the corpus striatum andproject fibers into the thalamus

Substantia nigra

melanin pigment

degenerates into Parkinsons disease

Subthalamic nucleus

yields ballistic movements, sudden limb jerks -

projectile movements


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Nuclei of the basal ganglia

capable of initiating and maintaining the fullrange of useful movements

Cerebellum Motor cortex

Autonomic cortex


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Association cortex

Basic organization of the brain

Three main processing blocks

1. Brainstem and the thalamic reticular activating

system2. Posterior cortex - integrates perception and

generates language

3. Frontal cortex - highest level - generatesprograms and executes plans


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Hemispheric lateralization of function

key feature of higher cortical processing

primary sensory cortices for touch, vision, hearing,smell and taste are represented bilaterally

e.g. Recognition of familiar faceslocalization of language

Limbic system

responsible for generating and modifying memoriesand for assigning emotional weight to sensory and

recalled experience Amygdala

one of the nucleus of the limbic system that receivesfibers from all sensory areas

serve as a gate for the assignment of emotional

significance to memories


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Regional functions of the brain

Frontal lobe Voluntary movement

Language production

Motor prosody

Comportment

Executive functions

Motivation

Temporal lobes

Audition Language

comprehension

Sensory prosody

Memory

Emotion

Parietal lobes Tactile sensation

Visuospatial function

Reading

Calculation

Occipital lobes Vision

Visual perception


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Ventral

tegmental area

Locus

ceruleus cerebellum

Inferior

colliculus

Superior

colliculus

Periaqueductal

gray area

Hippocampus

Arcuate

nucleusAmygdala

Nucleus

accumbens

Prefrontal

cortex

The Frontal Lobe

Bilateral lesions

Changes in personality howpersons interact with theworld

Frontal Lobe Syndrome

Slowed thinking, poorjudgment, decreased

curiosity, social withdrawal,irritability

Apathy to sudden impulsivedisinhibition

May be largely unnoticed,becoming apparent only under

unstructured, stressful, real-life situations

Trauma, infarcts, tumors,lobotomy, multiple sclerosis,Picks disease


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Localization of specific brain

functions

Arousal

Attention

Memory Language

Emotion


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Arousal and attention

Arousal

establishment and maintenance of awake sate

Brain regions: brainstem, ARAS, cortex

within the brainstem - ARAS - sets the level ofconsciousness

absence of which leads to stupor and coma

Attention

maintained by an intact right frontal lobe

the skill of maintaining a coherent line of thought isdistributed throughout the cortex

medical conditions that affect the cortex: loss ofskill, confusion and delirium


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Major causes of acute confusion

Infectious

Metabolic

Hypoxia

Hypoglycemia Uremia

Hepatic disease

Toxic

drugs

Vascular

stroke

SAH

Neoplastic Traumatic

brain injury


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Memory

Three periods with distinct anatomical correlates

Immediate memory

functions over a period of seconds

implicit in the concept of attention and abilityo follow train of thought

Recent memory

applies on the scale of minutes to days

working memory - ability to store information

and relate to cognitive information Remote memory

encompasses months to years


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Basic structures critical to the formation of thememory:

Medial temporal lobe

house the hippocampus

amygdala - rates the emotional importance ofan experience and to activate the level ofhippocampal activity

Diencephalic nuclei

Basal forebrain


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Hippocampus - significant site for the formationand storage of immediate and recent memories

left - efficient for forming verbal memories

right - non-verbal memories

Practice makes perfect - corticalization of motorcommands

memorized motor acts - activation of the mediantemporal lobe

with practice - left parietal cortex - highly skilledacts

Causes of amnesia: alcoholism, seizures,migraine, drugs, vitamin deficiencies, trauma,strokes, tumors, infections and degenerative

diseases


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Diencephalon - for formation of memory

dorsal medial nucleus of the thalamus

mamillary bodies


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Clinical disorder of memory

Alzheimers disease

most common clinical disorder of memory

char. by degeneration of neurons and theirreplacement by senile plaques and neurofibrillary

tangles impaired language comprehension and visuospatial

organization - parietal lobe

Korsakoffs syndrome

due to thiamine deficiency in chronic alcoholics

char. by severe inability to form new memories andinability to recall


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Language

Clearly demonstrates hemisphericlocalization of function

The dominant hemisphere for language

directs the dominant hand Language comprehension is processed at

three levels. Phonological processing- individual sounds

Lexical processingmatches the phonological

input with recognized words Semantic processing- connects the words to

their meaning


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Emotion

Derives from basic drives: feeding, sex, pleasure,pain, fear and aggression

Neuroanatomical basis: limbic system

other distinct human emotions: affection, pride,guilt, pity, envy, resentment - are learned andrepresented in the cortex


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The interplay of emotions is far beyond the

understanding of neuroanatomists.

Where are therepresentations of theid, ego and superego?

What are the

pathways for ethicaland moraljudgements?

What processes allowfor beauty to be in theeye of the beholder?


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Hemispheric dichotomy of

emotional representation

Left hemisphere - houses the analytical mind

Right hemisphere appears dominant for affect,socialization and body image

Left prefrontal cortex - appears to lift mood

Right prefrontal cortex - causes depression


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Limbic system

houses the emotional association areas whichdirects the hippocampus to express the motorand endocrine components of the emotional

state

Limbic system: Papez circuit (1937)

hippocampus, the fornix, the mamillarybodies, the anterior nucleus of the thalamus

and the cingulate gyrus


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Neurophysiology andNeurochemistry

- The study of the chemical interneuronalcommunication

- Basic electrophysiology

- Translation of the AP into chemicalneurotransmission


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Modified from Figure 15-12, Page 491 from:Essential Cell Biologyby Alberts et al. 1997, Garland Publishing Inc. New York, NY

1. Ion-Channel Linked Receptor


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(e.g) GABAAreceptor

NeuroscienceExploring the Brain2ndEdition 2001 by M.F. Bear, B.W. Connors & M.A. Paradiso. Lippincott, Williams &Wilkins, Baltimore MD, USA. ISBN: 0683-30596-4

Cl-


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Modified from Figure 15-14, Page 493 from:Essential Cell Biologyby Alberts et al. 1997, Garland Publishing Inc. New York, NY

2. G-Protein-Linked Receptor

The receptors: 7 transmembranesegments


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Neurotransmitters

Chemical signals that flow between neurons Chemical neurotransmission- is the process

involving the release of a neurotransmitters by

one neuron and the binding of theneurotransmitter molecule to a reecptor onanother neuron

anti- psychotics - block D2

anti-depressants - increase the amount of serotonin

or noepinephrine

N t itt th i


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1-9 Stahl S M, Essential

Psycho pharmacolog y (2000)

pre-propeptidegene

endoplasmicreticulum

primarymRNA

Pre-propeptide

mRNA prepropeptide

signal peptidase

propeptide

convertingenzyme

synapticvesicle

peptidepeptide

catabolicpeptidase

inactivemetabolite

Neurotransmitter synthesis


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Neurotransmitter and Human Behaviour

Biogenic Amines

Dopamine (schizophrenia)

Norepinephrine and Epinephrine(mood D/O, anxiety and panic states)

Serotonin (schizophrenia and affectivestates)


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Presynaptic components

Synthesis of all NT except the peptide NT which issynthesized in the cell bodies

NT synthesis is influenced by inclux of Ca+, levels

of cAMP and circulating hormones

Synapse

between the presynaptic and postsynapticmembranes

concentrations of the NTs in the synaptic cleft areregulated by feedback inhibition of the NT releaseand by reuptake into the presynaptic terminal bytransporter molecules


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Postsynaptic Components

NTs receptors are the sites of action for many of thepsychotherapeutic and psychoactive drugs

principal function: to alter the electrical

transmembrane potential: increase or decrease thelikelihood of AP

Excitatory NTs - cause depolarization of thepostsynaptic membrane

Sensitivity of receptors

no. of receptors present

the affinity of the receptor for the NT

efficiency with which the binding of the NT tothe receptor is translated into anintraneuronal message


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Types of Neurotransmitters

Biogenic amines

Dopamine

Norepinephrine

Epinephrine

Serotonin

Acetylcholine

Histamine

Amino acids

Peptides


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Biogenic amines

All biogenic amines NT are synthesized inthe axon terminal

Tryptophan

amino acid precursor of serotonin Tyrosine

amino acid precursor of thecatecholamines: D, NE, E


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Dopamine

Three most important dopaminergic tracts

nigrostriatal tract

cell bodies in the substantia nigracorpus striatum

D2 receptors in the caudate nucleus suppressthe activity of the caudate nucleus

caudate nucleus regulates motor acts bygating which intended acts are carried out

less - bradykinesia - Parkinsons

more - tics

mesolimbic-mesocortical tract

tuberoinfundibular tract


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Nigrostriatal tract

Mesolimbic-Mesocortical tract

cell bodies in the ventral tegmental area whichis adjacent to the SN, CC, and LS

mediate effects of anti-psychotic drugs

Tuberoinfundibular tract

arcuate nucleus and the periventircular areaof the hypothalamus and project to the

infundibulum and the anterior pittuitary D acts as a release -inhibiting factor of

prolactin in the anterior pitutitary


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Norepinephrine and Epinephrine

Noradrenergic and the adrenergic system

Life cycle

tyrosine dopamine

CNS noradrenergic tracts

project into the locus ceruleus in thepons

axons project through the medialforebrain bundle in the CC, LS,thalamus and hypothalamus

Tyrosine hydroxylase


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Amino acid

Contain the building blocks of protein

Brain: glutamate and aspartate

Two major AA:

GABA- Gamma-aminobutyric acid - inhibitoryamino acid (IAA); monocarboxylic amino acid

Glutamate -excitatory amino acid (EAA);dicarboxylic amino acid

several anti-convulsants act through the

GABAergic mechanisms


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Glutamate synthesized from glucose and glutamine in the

presynaptic neuron terminals and stored in thesynaptic vesicles

primary NT in cerebellar granule cells, thestriatum, the cells of the hippocampus

its release is stimulated by nicotine

Glutamate receptors:

N-methyl-D-aspartate (NMDA) receptor-plays an essential role in learning andmemory as well in psychopathology


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GABA found most exclusively in the CNS and does

not cross the BBB

midbrain and diencephalon, less in the cerebralhemispheres, the pons, and the medulla

synthesized from glutamate by the ratelimiting enzyme glutamic acid carboxylase(GAD) which requires pyridoxine (Vit. B6) as

cofactor is the primary NT in intrinsic neurons that

function as local mediators for the inhibitoryfeedback loops


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Peptides

refers to the chemical bond between thecarboxylic acid group and the amino group ofadjacent amino acids in a protein

differ from other NT because they aremanufactured in the cell body

may serve as neuromodulary role at somesynapses


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Neurobiological Basis of Human Behavior