The Brain and Human

Behavior
Dr. Rene V. Yat
Parts of basal ganglia
The brain structures that comprise
The Basal Ganglia
Putamen,
Caudate nucleus,
Globus pallidus
Substantia nigra
Subthalamic nucleus of Luys
Conditions that cause basal ganglia
dysfunction
Drug overdose
Head injury
Infection
Liver disease
Metabolic processes
Multiple sclerosis
Stroke
Tumours
Side effects of medications
Brain Disorders associated with
Basal ganglia dysfunction
Dystonias
Huntington’s disease
Parkinson’s disease
Supranuclear Palsy
Wilson’s disease
The dopamine pathways in schizophrenia

In schizophrenia there is an increase in dopamine

transmission 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.
The glutamate pathways in a brain affected by schizophren

In the normal brain the prominent glutaminergic

pathways 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, subthalamic
nucleus 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.
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 dopaminergic
system, 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.
 NEUROTRANSMITTERS
Biogenic amines
Amino acids
Peptides
 NEUROTRANSMITTERS
Biogenic amines
Dopamine
Norepinephrine
Epinephrine
Serotonin
Histamine
Acetylcholine
 NEUROTRANSMITTERS
Amino Acids
Amino acids are the most
abundant neurotransmitters in the brain.
Nichols suggested: “amino acids synapses
exceed those of all the other
neurotransmitters combined…amino acids
are responsible for almost all the fast
signaling between neurons, leaving
predominantly modulatory roles for the
other transmitters.”
 Amino acid
NEUROTRANSMITTERS
The second neurotransmitter family is composed
of amino acids, organic compounds containing
both an amino group (NH2) and a carboxylic acid
group (COOH). Amino acids that serve as
neurotransmitters include glycine, glutamic and
aspartic acids, and gamma-amino butyric acid
(GABA). Glutamic acid and GABA are the most
abundant neurotransmitters within the central
nervous system, and especially in the cerebral
cortex, which is largely responsible for such higher
brain functions as thought and interpreting
sensations
 NEUROTRANSMITTERS
Amino Acids
Glutamate
GABA
Glycine
L-Arginine
 NEUROTRANSMITTERS
Amino Acids
Glutamate is the major excitatory neurotransmitter
and is distributed in all regions of the brain.
Aspartate is closely related to glutamate and the
two amino acids are often found together at axon
terminals. Neurons synthesize glutamate and
aspartate and are independent of dietary supply.
 NEUROTRANSMITTERS
Amino Acids
Gamma amino butyric acid (GABA) is the major
inhibitory neurotransmitter in the brain, derived
from glucose, which is transaminated in the Kreb’s
cycle to glutamine and then converted to GABA by
the enzyme, glutamic acid decarboxylase. The
production of GABA appears to be independent of
the dietary supply of glutamine but requires dietary
pyridoxine
 NEUROTRANSMITTERS
Amino Acids
Glycine is an inhibitory neurotransmitter found
mostly in the brain stem and spinal cord. A major
discovery that adds complexity to the already
confusing story of neurotransmitters is that glycine
acts as a co-transmitter in excitatory NMDA
synapses.
 NEUROTRANSMITTERS
Amino Acids
L-Arginine is the precursor of endogenous nitric oxide (NO),
which is a vasodilator acting via the intracellular second-
messenger cGMP. In healthy humans, L-arginine induces
peripheral vasodilation and inhibits platelet aggregation due
to an increased NO production. Prostaglandin E1 (PGE1)
induces peripheral vasodilation via stimulating prostacyclin
receptors.
A mixture of branch-chain amino acids, leucine, valine and
isoleucine will reduce tardive dyskinesia and movement
disorder that is caused by anti-schizophrenic drugs. Tarvil,
has been marketed in the USA that delivers 6.0 grams of the
3 amino acids per packet. A dose of 6 gm three times a day
has been recommended.
 Neuropeptides
Function of Neuropeptides:

There are cells in the brain that produce various neuropeptides, and
these 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.
Characteristics of Neuropeptides:

Peptides are compounds consisting of two or more amino acids (the

building 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.
 PEPTIDES
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
Neuropeptide Y
GABA
Somatostatin (in the hippocampus)
Cholecystokinin
Neuropeptide Y (in the arcuate nucleus)
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
Dopamine
Cholecystokinin
Neurotensin
Epinephrine (adrenaline)
Neuropeptide Y
Neurotensin
Serotonin (5-HT)
Substance P
TRH
Enkephalin
UPREGULATION HYPOTHESIS OF NEURONAL RECEPTORS
 Upregulation theory

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 of
stimulation by synthesizing additional receptor sites. This
process is known as up-regulation.
 DESENSITIZATION THEORY

By increasing the amount of neurotransmitter in

the cleft, you can normalize responsiveness.
Increased neurotransmitter increases stimulation
of receptor sites, which prompts the postsynaptic
neuron to compensate by decreasing receptor
sensitivity, a process known as desensitization
 Downregulation hypothesis

The postsynaptic neuron is also thought to compensate

for increasing stimulation by decreasing the number of
receptor sites, a process known as down-regulation.
“Prolonged sitting can cause
ischial bursitis”.
“To study medicine without books and
mentors is like a shaman who professes
who know everything but deep inside he
knows nothing at all.
You can shake, rattle, and roll. But at the
end of the day, you wish that you have
studied hard for the life you are handling in
front of you is not a guinea pig at all”.
END OF THE LECTURE