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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.aspx8/14/2019 Brain & Human Behaviour
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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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NEUROTRANSMITTERSNEUROTRANSMITTERS
Biogenic aminesBiogenic amines
DopamineDopamine
NorepinephrineNorepinephrineEpinephrineEpinephrine
SerotoninSerotonin
HistamineHistamineAcetylcholineAcetylcholine
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NEUROTRANSMITTERSNEUROTRANSMITTERS
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
NEUROTRANSMITTERSNEUROTRANSMITTERS
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.html8/14/2019 Brain & Human Behaviour
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NEUROTRANSMITTERSNEUROTRANSMITTERS
Amino AcidsAmino AcidsGlutamateGlutamate
GABAGABA
GlycineGlycine
L-ArginineL-Arginine
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NEUROTRANSMITTERSNEUROTRANSMITTERS
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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NEUROTRANSMITTERSNEUROTRANSMITTERS
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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NEUROTRANSMITTERSNEUROTRANSMITTERS
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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NEUROTRANSMITTERSNEUROTRANSMITTERS
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/Norepinephrine8/14/2019 Brain & Human Behaviour
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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/Dopamine8/14/2019 Brain & Human Behaviour
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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