BRAIN AND BEHAVIOR

PSYCHIATRY I
Neurophysiology and Neurochemistry

• Each neuron that multiple inputs are

integrated to affect processes including
gene expression, synapse formation, and
neuronal firing rates and patterns.
• Single neurons communicate by
interpreting their chemical environment, by
instantly changing the chemical cues to
electrical activity for transport down axons.
• Finally, by efficiently translating the
electrical data into finely modulated
chemical emissions that can be secreted
to influence other neuronal or nonneuronal
cells
• The electrical impulses facilitate
instantaneous responses, and the
chemical environment is important in
maintaining the fidelity of the brain's image
of the world.
 Neurophysiology and
Neurochemistry
• Neurochemistry - The study of chemical
interneuronal communication
• Cells also contained inhibitory and
excitatory receptive substances.
• Basic apparatus of chemical
neurotransmission: neurotransmitters
and specific receptor molecules.
• Neuronal electrical activity is continuously
modulated by excitatory and inhibitory
neurotransmitters.
• Neuronal electrical activity, along with the
chemical factors, simultaneously modifies
the abundance and phosphorylation status
of cellular proteins, the level of expression
of certain genes, and the connectivity of a
neuron to thousands of neighboring
neurons.
 Basic Electrophysiology
Membranes and Charge
In the resting state, the intracellular
compartment of a neuron is more negatively
charged than the extracellular compartment

The principal ion channels are the sodium,

potassium, calcium, and chloride ion
channels.

The membrane is semipermeable because it

is selective regarding which ions can pass
through it.
• Ion Channels - protein pores of the
membrane allows flow of ions (K, Na, CL)
during changes in membrane potential
which occur when the charge gradients
maintained by the insulator function of the
membrane are allowed to flow unimpeded
through it.
• Action potentials - instantaneous
changes in membrane potential
• At the synaptic terminus of the axon,
action potentials trigger the release of
neurotransmitters into the synaptic cleft,
where they may act on other neurons or
muscles.
• Synapses - site at which stimuli are given
and received and where the finest
shadings of neuronal activity are
negotiated
Components:
axon terminal of the presynaptic neuron,
synaptic cleft
dendrite of the postsynaptic neuron.
 Criteria for a Neurotransmitter
• The molecule is synthesized in the neuron.
• The molecule is present in the presynaptic
neuron and is released on depolarization in
physiologically significant amounts.
• When administered exogenously as a drug,
the exogenous molecule mimics the effects
of the endogenous neurotransmitter.
• A mechanism in the neurons or the synaptic
cleft acts to remove or deactivate the
neurotransmitter.
• The three major types of neurotransmitters
in the brain :
Biogenic amines
Amino acids
Peptides
Biogenic Amines - neurotransmitters is
synthesized in a discrete nucleus of
neurons from which axons project widely
throughout the brain and spinal cord.
• Exert influence on the activity of the brain,
and they are of central importance to the
pharmacological therapy of thought, mood,
and anxiety disorders.
Biogenic Amines:
Dopamine, norepinephrine, and
epinephrine are products of the
catecholamine synthetic pathway.

Serotonin, acetylcholine, and histamine

are derived from distinct precursors.
• Dopamine
CNS Dopaminergic Tracts:
nigrostriatal tract
mesolimbic-mesocortical tract
tuberoinfundibular tract
• The dopaminergic axon terminal is the site
of synthesis for dopamine.
• Dopamine is one of the three
catecholamine neurotransmitters that are
synthesized, starting with the amino acid
tyrosine.
• The rate-limiting enzymatic step in the
synthesis of any of the catecholamines is
catalyzed by tyrosine hydroxylase.
• The actions of dopamine are terminated by two
general routes.
Dopamine can be taken back up into the
presynaptic neuron and recycled as a
neurotransmitter – REUPTAKE MECHANISM
Dopamine can be metabolized by enzymes
monoamine oxidase (MAO) and catechol-O-
methyltransferase (COMT).
• Dopamine and Drugs
antipsychotic compounds has been
correlated with their affinity for the D2
receptor. Because blockade of dopamine
receptors, particularly the D2 receptor, has
been associated with the efficacy of
antipsychotic drugs,
• Dopamine hypothesis of schizophrenia
drugs that block dopamine receptors
(e.g., haloperidol) have antipsychotic
activity and drugs that stimulate dopamine
activity (e.g., amphetamine) can induce
psychotic symptoms in nonschizophrenic
persons when given in sufficiently high
doses.
• The norepinephrine system and the
epinephrine system are also referred to
as the noradrenergic system and the
adrenergic system, respectively
• CNS Noradrenergic Tracts
The major concentration of noradrenergic
(and adrenergic) cell bodies that project
upward in the brain is in the compact
locus ceruleus in the pons
• Psychiatric drugs associated with
norepinephrine the classic antidepressant
drugs, the tricyclic drugs and the MAO
inhibitors (MAOIs), and, more recently,
venlafaxine (Effexor), mirtazapine
(Remeron)
• Mirtazapine acts by blocking presynaptic
alpha-adrenergic receptors - removing
the feedback inhibition normally exerted
on the release of norepinephrine
• Net effect of mirtazapine is to increase
norepinephrine secretion.
• Serotonin
CNS Serotonergic Tracts
The major site of serotonergic cell
bodies is in the upper pons and the
midbrain specifically, the median and
dorsal raphe nuclei . These neurons
project to the basal ganglia, the limbic
system, and the cerebral cortex
• Serotonin is synthesized in the axonal
terminal
• The precursor amino acid is tryptophan.
and the availability of tryptophan is the
rate-limiting function, and the enzyme
tryptophan hydroxylase is not rate limiting
• Serotonin receptors are 5-HT
• The principal association of serotonin with
a psychopathological condition is with
depression
• Histamine
Blockade of H1 receptors is the
mechanism of action for allergy
medications and is partly the mechanism
for commonly observed side effects (e.g.,
sedation, weight gain, and hypotension) of
some psychotropic drugs.
• Acetylcholine
CNS Cholinergic Tracts
group of cholinergic neurons in the
nucleus basalis of Meynert projects to the
cerebral cortex and the limbic system.
The two cholinergic receptors are
muscarinic and nicotinic
Anticholinergic drugs useful for treatment
of the motor abnormalities caused by the
use of classic antipsychotic drugs (e.g.,
haloperidol).
• The most common association with
acetylcholine is dementia of the
Alzheimer's type and other dementias.
• Anticholinergic agents can impair learning
and memory in healthy people.
• Acetylcholine may also be involved in
mood and sleep disorders.
Peptide Neurotransmitters
As many as 300 peptide neurotransmitters
may be in the human brain
Peptide is a short protein consisting of fewer
than 100 amino acids.
Peptides are made in the neuronal cell body
by the transcription and translation of a
genetic message. e action of enzymes,
peptidases, which
• Substance P - associated with mediation
of the perception of pain.
• Neurotensin - involved in the
pathophysiology of schizophrenia
• Somatostatin - growth hormone-inhibiting
factor, implicated somatostatin in
Huntington's disease and dementia of the
Alzheimer's type.
• Vasopressin and oxytocin - involved in the
regulation of mood and most recently,
social behavior.
• Neuropeptide Y – stimulate appetite.
• Amino Acid Neurotransmitters

Amino acids - building blocks of proteins.

Because of their abundance,

Two major amino acid neurotransmitters are

GABA is an inhibitory amino acid
Glutamate is an excitatory amino acid.
Psychoneuroendocrinology
• refers to the structural and functional
relations between the hormonal system and
the central nervous system (CNS) and the
behaviors that modulate and arise from both.
• thyroid hormones essential for the normal
development of the CNS, deficiency during
postnatal life, impair growth and
development of the brain, resulting in
behavioral disturbances that may be
permanent if replacement therapy is not
instituted
• Insulin - depression is frequent in patients
with diabetes, as are indexes of impaired
hormonal response to stress.
Some antipsychotics are known to
dysregulate insulin metabolism.
Psychoneuroimmunology
• The nervous system and the immune
system represent two networks within the
body and considered to act as parallel but
independent entities.
• stressful life events can increase the
susceptibility to infectious diseases
• decreases in measures of immune
function in persons exposed to chronic life
stressors, such as divorce and taking care
of patients with Alzheimer's disease.
• Altered CNS function results from a
combination of the direct effects of an
injurious event on various cell types and
the effects of inflammatory mediators on
neurons and supporting cells is a
cornerstone of neuroimmunology
Neurogenetics

• Many major psychiatric disorders have

been shown to have a strong hereditary
predisposition.
• In the case of schizophrenia, for example,
a first-degree relative of an affected
patient has about a 10 percent chance of
having the illness.
• Traits are clinically defined features, such
as sickle crises in sickle cell anemia or
blue eyes.
• Some traits are determined by a single
gene, whereas others emerge from the
interactions of the products of (in some
cases) hundreds of genes.
• Behavior likely is the expression of the
products of thousands of genes, although
specific single-gene mutations may
influence certain behaviors in consistent
ways
• behavioral traits can result from either
genetics (nature) or upbringing (nurture),
 SUMMARY
• Chemical Neurotransmission from the
presynaptic neuron can trigger postsynaptic
reaction.
• The process of chemical neurotransmission
is a candidate for modification by drugs
• Most psychotropics drugs acto on the
process of chemical neurotransmisison at the
level of the NT, enzymes and receptors
• Future psychotropics drugs will act directly
on the biochemical cascades those elements
that control pre/post synaptic genes
• The neuron is dynamically modifying its
synaptic connections throughout its life
in response to learning, life experiences,
genetic programming, drugs and diseases;
chemical neurotransmission is the key
aspect to the regulation of these important
precesses.
QUESTIONS