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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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8/12/2019 Neurobiological Basis of Human Behavior
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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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Thank you very much!