brain & human behaviour

8/14/2019 Brain & Human Behaviour

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Dr. Rene V. YatDr. Rene V. Yat

The Brain and HumanThe Brain and Human

BehaviorBehavior


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Parts of basal gangliaParts of basal ganglia


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The brain structures that compriseThe brain structures that comprise

The Basal GangliaThe Basal Ganglia

Putamen,Putamen,

Caudate nucleus,Caudate nucleus,

Globus pallidusGlobus pallidusSubstantia nigraSubstantia nigra

Subthalamic nucleus of LuysSubthalamic nucleus of Luys


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Conditions that cause basal gangliaConditions that cause basal ganglia

dysfunctiondysfunction

Drug overdoseDrug overdose

Head injuryHead injury

InfectionInfection

Liver diseaseLiver diseaseMetabolic processesMetabolic processes

Multiple sclerosisMultiple sclerosis

StrokeStrokeTumoursTumours

Side effects of medicationsSide effects of medications


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Brain Disorders associated withBrain Disorders associated with

Basal ganglia dysfunctionBasal ganglia dysfunction

DystoniasDystonias

Huntingtons diseaseHuntingtons disease

Parkinsons diseaseParkinsons diseaseSupranuclear PalsySupranuclear Palsy

Wilsons diseaseWilsons disease


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The dopamine pathways in schizophrenia

In schizophrenia there is an increase in dopaminetransmission between the substantia nigra to the

caudate nucleus-putamen (neostriatum) compared

with normal. While in the other major dopaminergic

pathways to the mesolimbic forebrain and the

tubero-infundibular system dopamine

transmission is reduced. The dopamine hypothesis

of schizophrenia proposes that increased levels of

dopamine or dopamine receptors in the dorsal and

or ventral striatum underlie the disorder.


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The glutamate pathways in a brain affected by schizophr

In the normal brain the prominent glutaminergicpathways are: the cortico-cortical pathways; the

pathways between the thalamus and the cortex; and

the extrapyramidal pathway (the projections between

the cortex and striatum). Other glutamate projections

exist between the cortex, substantia nigra, subthalamicnucleus and pallidum. The glutaminergic pathways are

hypoactive in the brains of people diagnosed with

schizophrenia and this is thought to cause the

confusion and psychosis associated with the disorder.
http://www.cnsforum.com/imagebank/item/Neuro_path_GLUT_SCH/default.aspxhttp://www.cnsforum.com/imagebank/item/Neuro_path_GLUT_SCH/default.aspx


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The serotonergic pathway showing the effects

of schizophrenia

The two key serotonergic pathways in schizophrenia

are the projections from the dorsal raphe nuclei into the

substantia nigra and the projections from the rostral

raphe nuclei ascending into the cerebral cortex, limbic

regions and basal ganglia. The up-regulation of these

pathways leads to hypofunction of the dopaminergicsystem, and this effect may be responsible for the

negative symptoms of schizophrenia. The serotonergic

nuclei in the brainstem that give rise to descending

serotonergic axons remain unaffected in schizophrenia.


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NEUROTRANSMITTERSNEUROTRANSMITTERS

Biogenic aminesBiogenic amines

Amino acidsAmino acids

PeptidesPeptides


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Biogenic aminesBiogenic amines

DopamineDopamine

NorepinephrineNorepinephrineEpinephrineEpinephrine

SerotoninSerotonin

HistamineHistamineAcetylcholineAcetylcholine


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Amino AcidsAmino Acids

Amino acids are the mostAmino acids are the most

abundant neurotransmitters in the brain.abundant neurotransmitters in the brain.

Nichols suggested: amino acids synapsesNichols suggested: amino acids synapsesexceed those of all the otherexceed those of all the other

neurotransmitters combinedamino acidsneurotransmitters combinedamino acids

are responsible for almost all the fastare responsible for almost all the fast

signaling between neurons, leavingsignaling between neurons, leaving

predominantly modulatory roles for thepredominantly modulatory roles for the

other transmitters.other transmitters.


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Amino acidAmino acid


The second neurotransmitter family is composedThe second neurotransmitter family is composed

ofofamino acidsamino acids, organic compounds containing, organic compounds containing

both an amino group (NH2) and a carboxylic acidboth an amino group (NH2) and a carboxylic acid

group (COOH). Amino acids that serve asgroup (COOH). Amino acids that serve as

neurotransmitters include glycine, glutamic andneurotransmitters include glycine, glutamic andaspartic acids, and gamma-amino butyric acidaspartic acids, and gamma-amino butyric acid

(GABA). Glutamic acid and GABA are the most(GABA). Glutamic acid and GABA are the most

abundant neurotransmitters within the centralabundant neurotransmitters within the central

nervous system, and especially in the cerebralnervous system, and especially in the cerebralcortex, which is largely responsible for such highercortex, which is largely responsible for such higher

brain functions as thought and interpretingbrain functions as thought and interpreting

sensationssensations
http://encarta.msn.com/encyclopedia_761555775/Amino_Acids.htmlhttp://encarta.msn.com/encyclopedia_761555775/Amino_Acids.htmlhttp://encarta.msn.com/encyclopedia_761555775/Amino_Acids.htmlhttp://encarta.msn.com/encyclopedia_761555775/Amino_Acids.html


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Amino AcidsAmino AcidsGlutamateGlutamate

GABAGABA

GlycineGlycine

L-ArginineL-Arginine


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Amino AcidsAmino AcidsGlutamateGlutamate is the major excitatory neurotransmitteris the major excitatory neurotransmitter

and is distributed in all regions of the brain.and is distributed in all regions of the brain.

Aspartate is closely related to glutamate and theAspartate is closely related to glutamate and thetwo amino acids are often found together at axontwo amino acids are often found together at axon

terminals. Neurons synthesize glutamate andterminals. Neurons synthesize glutamate and

aspartate and are independent of dietary supply.aspartate and are independent of dietary supply.


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Amino AcidsAmino AcidsGamma amino butyric acid (GABA)Gamma amino butyric acid (GABA) is the majoris the major

inhibitory neurotransmitter in the brain, derivedinhibitory neurotransmitter in the brain, derived

from glucose, which is transaminated in the Krebsfrom glucose, which is transaminated in the Krebscycle to glutamine and then converted to GABA bycycle to glutamine and then converted to GABA by

the enzyme, glutamic acid decarboxylase. Thethe enzyme, glutamic acid decarboxylase. The

production of GABA appears to be independent ofproduction of GABA appears to be independent of

the dietary supply of glutamine but requires dietarythe dietary supply of glutamine but requires dietary

pyridoxinepyridoxine


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Amino AcidsAmino AcidsGlycineGlycine is an inhibitory neurotransmitter foundis an inhibitory neurotransmitter found

mostly in the brain stem and spinal cord. A majormostly in the brain stem and spinal cord. A major

discovery that adds complexity to the alreadydiscovery that adds complexity to the alreadyconfusing story of neurotransmitters is that glycineconfusing story of neurotransmitters is that glycine

acts as a co-transmitter in excitatory NMDAacts as a co-transmitter in excitatory NMDA

synapses.synapses.


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Amino AcidsAmino AcidsL-ArginineL-Arginine is the precursor of endogenous nitric oxide (NO),is the precursor of endogenous nitric oxide (NO),which is a vasodilator acting via the intracellular second-which is a vasodilator acting via the intracellular second-messenger cGMP. In healthy humans, L-arginine inducesmessenger cGMP. In healthy humans, L-arginine inducesperipheral vasodilation and inhibits platelet aggregation dueperipheral vasodilation and inhibits platelet aggregation due

to an increased NO production. Prostaglandin E1 (PGE1)to an increased NO production. Prostaglandin E1 (PGE1)induces peripheral vasodilation via stimulating prostacyclininduces peripheral vasodilation via stimulating prostacyclinreceptors.receptors.

A mixture of branch-chain amino acids, leucine, valine andA mixture of branch-chain amino acids, leucine, valine andisoleucine will reduce tardive dyskinesia and movementisoleucine will reduce tardive dyskinesia and movement

disorder that is caused by anti-schizophrenic drugs. Tarvil,disorder that is caused by anti-schizophrenic drugs. Tarvil,has been marketed in the USA that delivers 6.0 grams of thehas been marketed in the USA that delivers 6.0 grams of the3 amino acids per packet. A dose of 6 gm three times a day3 amino acids per packet. A dose of 6 gm three times a dayhas been recommended.has been recommended.


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Neuropeptides

Function of Neuropeptides:

There are cells in the brain that produce various neuropeptides, andthese neuropeptides do just about everything.

They can be either pro-inflammatory or anti-inflammatory, with anti-

inflammatory being preferred. They are responsible for many

functions:

They control our mood, energy levels, pain and pleasure reception,

body weight, and ability to solve problems; they also form memories

and regulate our immune system.

These active little messengers in the brain actually turn on cellular

function in the skin.


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Characteristics of Neuropeptides:

Peptides are compounds consisting of two or more amino acids (thebuilding blocks of proteins), chained together by what is called a

peptide bond.

Neuropeptides are peptides released by neurons (brain cells) as

intercellular messengers. Some neuropeptides function as

neurotransmitters, and others function as hormones.

Peptides and neuropeptides, like many substances in our bodies (think

cholesterol) can work both for and against us. Anti-inflammatory

neuropeptides work for us to reduce inflamation fo the skin.


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Transmitter names are shown in bold.

Norepinephrine (noradrenaline). In neurons of the

A2 cell group in the nucleus of the solitary tract),

norepinephrine co-exists with:Galanin

Enkephalin

NeuropeptideY

GABA

Somatostatin (in the hippocampus)Cholecystokinin

NeuropeptideY (in the arcuatenucleus)

Acetylcholine

VIP

Substance P - Originally nown as Tachykinins.Because they are rapidly absorbed they now known as

neurokinins. They play a key role in modulation of

pain and emotions. Hence possibly in the future this

could be a source of new antidepresants

PEPTIDES
http://en.wikipedia.org/wiki/Norepinephrinehttp://en.wikipedia.org/wiki/Nucleus_of_the_solitary_tracthttp://en.wikipedia.org/wiki/Galaninhttp://en.wikipedia.org/wiki/Enkephalinhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/Somatostatinhttp://en.wikipedia.org/wiki/Hippocampushttp://en.wikipedia.org/wiki/Cholecystokininhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Arcuate_nucleushttp://en.wikipedia.org/wiki/Arcuate_nucleushttp://en.wikipedia.org/wiki/Acetylcholinehttp://en.wikipedia.org/wiki/Vasoactive_intestinal_peptidehttp://en.wikipedia.org/wiki/Substance_Phttp://en.wikipedia.org/wiki/Substance_Phttp://en.wikipedia.org/wiki/Vasoactive_intestinal_peptidehttp://en.wikipedia.org/wiki/Acetylcholinehttp://en.wikipedia.org/wiki/Arcuate_nucleushttp://en.wikipedia.org/wiki/Arcuate_nucleushttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Cholecystokininhttp://en.wikipedia.org/wiki/Hippocampushttp://en.wikipedia.org/wiki/Somatostatinhttp://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Enkephalinhttp://en.wikipedia.org/wiki/Galaninhttp://en.wikipedia.org/wiki/Nucleus_of_the_solitary_tracthttp://en.wikipedia.org/wiki/Norepinephrine


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Dopamine

CholecystokininNeurotensin

Epinephrine (adrenaline)

NeuropeptideY

NeurotensinSerotonin (5-HT)

Substance P

TRH

Enkephalin

PEPTIDES
http://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Cholecystokininhttp://en.wikipedia.org/wiki/Neurotensinhttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Neurotensinhttp://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Substance_Phttp://en.wikipedia.org/wiki/Enkephalinhttp://en.wikipedia.org/wiki/Enkephalinhttp://en.wikipedia.org/wiki/Substance_Phttp://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Neurotensinhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Neuropeptide_Yhttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Neurotensinhttp://en.wikipedia.org/wiki/Cholecystokininhttp://en.wikipedia.org/wiki/Dopamine


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UPREGULATION HYPOTHESIS OF NEURONAL RECEPTORS


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Supersensitivity is a compensatory response of the

postsynaptic neuron when it receives too little stimulation.

The neuron tries to make up for a lack of stimulation by

increasing receptor responsiveness. Over time, the

postsynaptic neuron may also compensate for lack ofstimulation by synthesizing additional receptor sites. This

process is known as up-regulation.

Upregulation theory


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By increasing the amount of neurotransmitter in

the cleft, you can normalize responsiveness.

Increased neurotransmitter increases stimulationof receptor sites, which prompts the postsynaptic

neuron to compensate by decreasing receptor

sensitivity, a process known as desensitization

DESENSITIZATION THEORY


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The postsynaptic neuron is also thought to compensate

for increasing stimulation by decreasing the number of

receptor sites, a process known as down-regulation.

Downregulation hypothesis


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Prolonged sitting can causeProlonged sitting can cause

ischial bursitis.ischial bursitis.


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To study medicine without books andTo study medicine without books and

mentors is like a shaman who professesmentors is like a shaman who professeswho know everything but deep inside hewho know everything but deep inside he

knows nothing at all.knows nothing at all.

You can shake, rattle, and roll. But at theYou can shake, rattle, and roll. But at theend of the day, you wish that you haveend of the day, you wish that you have

studied hard for the life you are handling instudied hard for the life you are handling in

front of you is not a guinea pig at all.front of you is not a guinea pig at all.


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END OF THE LECTUREEND OF THE LECTURE

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