The mere mention of

Psychiatry evokes an
esoteric almost non-
medical aura but it is
inevitable specially as
we progress that we
realize the biological
substrate which has
always been there –
the brain
The Brain and
Behaviour

Joge Los Baños, MD

 Functional Neuroanatomy
• Sensory System – process external stimuli

• Association Units – integrates sensory input

with internal drivers and emotional stimuli

• Motor System – manipulates external

environment
 Sensory Systems
• Somatosensory
(light touch, pressure, pain, temperature,
vibration, proprioception)
• Visual (see)
• Auditory (hear)
• Olfactory (smell)
• Gustatory (taste)
 Two Paradigms on the formation of
the final synaptic arrangement
1. Genetics and Experience / Nature and Nurture

– Fiber projection arrangment organized by fixed and diffusible

chemical cues
– modeling and remodeling on the basis of coordinated neural activity
(activity-dependent formation of synaptic connectivity)

4. Presence of highly specialized brain cells that respond

exclusively to extremely specific stimuli (cellular
localization of specific feature extraction) e.g. “grandmother
cell”
 Somatotropic
organization of the
Somatosensory System
Fiber Sorting after entry to spinal cord
1. Synapse within one or two spinal segments
2. Conscious perception of touch, temperature,
pain, decussate on entry and ascend through
spinothalamic tract
• Lateral spinothalamic: localized, discrete, acute pain
• Medial spinothalamic and spinoreticulothalamic :
diffuse, chronic pain
3. Conscious perception of touch, proprioception,
vibration ascend without immediate decussation
through the posterior columns
• All somatosensory fibers project to, and
synapse in, the thalamus
• The thalamic neurons preserve the
somatotropic representation by projecting
fibers to the somatosensory cortex
Somatotropic
map
 Psychiatric implications
• Reciprocal connections in the
somatosensory system specifically fibers
that project from and to the thalamus and
cortex serve to filter sensory input but in
pathological states may underlie
psychosomatic syndromes as conversion
disorders.
Visual System
 Central Visual Pathway
• Once the ganglion cell axons leave the retina, they travel
through the optic nerve to the optic chiasm, a partial
crossing of the axons.
• At the optic chiasm the left and right visual worlds are
separated.
• After the chiasm, the fibers are called the optic tract.
• The optic tract wraps around the cerebral peduncles of the
midbrain to get to the lateral geniculate nucleus (LGN).
• The LGN is really a part of the thalamus, and remember
that nothing gets up to cortex without synapsing in
thalamus first
• Almost all of the optic tract axons, therefore, synapse in the
LGN.
• The remaining few branch off to synapse in nuclei of the
midbrain: the superior colliculi and the pretectal area.
 Central Visual Pathway
• The neurons in the LGN send their axons directly to V1
(primary visual cortex, striate cortex, area 17) via the optic
radiations.
• This highway of visual information courses through the
white matter of the temporal and parietal lobes, and can be
very vulnerable to strokes.
• Once the axons reach V1, they terminate primarily in a
single sub-layer of cortex.
• As the signal is transmitted to upper layers of cortex, the
information from the two eyes is mixed and binocular
vision is created
• but in yet another layer the two eyes are still entirely
separate. Therefore, if you could label the inputs from a
single eye, you would see little pillars of label which line
up next to each other and form tiger stripes. These are the
ocular dominance stripes. (stereoscopic localization)
 Central Visual Pathway
• Primary visual cortex: lines of specific orientation

• Secondary visual cortex: particular movements and angles

• Inferior temporal Cortex (ITC): shape, form, and color

• Posterior parietal Cortex: location, motion, and distance

• Left ITC: facial features

• Right ITC: complex shapes

 Disorders of Visual Perception
• Prosopagnosia (inability to recognize faces)
• Apperceptive Visual Agnosia
– (inability to identify and draw from visual cues)
• Associative Visual Agnosia
– (inability to name or use objects despite ability to use them)
• Color agnosia (inability to recognize color)
• Color anomia (inability to name color)
• Central achromatopsia
– (complete inability to perceive color)
• Anton’s syndrome (inability to acknowledge blindness)
• Balint’s syndrome
– (optic ataixa, oculomotor apraxia, simultagnosia)
• Gertmann’s syndrome
– (agraphia, aclaculia, right-left disorientation, finger agnosia)
Auditory
System
 Auditory Pathway
• The auditory nerve carries the signal into the brainstem and synapses
in the cochlear nucleus.
• From the cochlear nucleus, auditory information is split into at least
two streams
• Auditory nerve fibers going to the ventral cochlear nucleus synapse
on their target cells with preservation of the timing of the signal to the
microsecond.
• The ventral cochlear nucleus cells then project to a collection of nuclei
in the medulla called the superior olive.
• In the superior olive, the minute differences in the timing and loudness
of the sound in each ear are compared, and from this you can
determine the direction the sound came from.
• The superior olive then projects up to the inferior colliculus via a
fiber tract called the lateral lemniscus.
 Auditory Pathway
• The second stream of information starts in the
dorsal cochlear nucleus.
• Unlike the exquisitely time-sensitive localization
pathway, this stream analyzes the quality of
sound.
• The dorsal cochlear nucleus, with fairly complex
circuitry, picks apart the tiny frequency
differences which make "bet" sound different from
"bat" and "debt".
• This pathway projects directly to the inferior
colliculus, also via the lateral lemniscus.
 Summary of the Auditory Pathway
• Fibers from the cochlear nuclei and the superior
olive (not the inferior) travel up the lateral
lemniscus (not the medial) to the inferior
colliculus (not the superior), and then to the
medial geniculate (not the lateral) in the thalamus
which projects to primary auditory cortex,
located on the banks of the temporal lobes.
• Try remembering the mnemonic, "S-L-I-M" .
 Olfactory System
• The axons from all the thousands of cells expressing the
same odor receptor converge in the olfactory bulb. Mitral
cells in the olfactory bulb send the information about the
individual features to other parts of the olfactory system in
the brain, which puts together the features into a
representation of the odor.
• Since most odor molecules have many individual features,
the combination of features gives the olfactory system a
broad range of odors that it can detect.
• Odor information is easily stored in long term memory and
has strong connections to emotional memory.
• This is possibly due to the olfactory system's close
anatomical ties to the limbic system and hippocampus, areas
of the brain that have long been known to be involved in
emotion and place memory, respectively.
Olfactory Tract and Central Pathways
• Mitral cell axons project to the olfactory cortex via the
olfactory tract.
• Medial fibers of the tract contact the anterior olfactory
nucleus and the septal area.
• Some fibers project to the contralateral olfactory bulb via
the anterior commissure.
• Lateral fibers contact third-order neurons in the primary
olfactory cortex (prepyriform and entorhinal areas)
directly.
• Third-order neurons send projections to the dorsomedial
nucleus of the thalamus, the basal forebrain, and the limbic
system.
Olfactory Tract and Central Pathways
• The thalamic connections are thought to serve as a
conscious mechanism for odor perception, while
the amygdala and the entorhinal area are limbic
system components and may be involved in the
affective components of olfaction.
• Investigations of regional cerebral blood flow
have demonstrated a significant increase in the
amygdaloid nucleus with the introduction of a
highly aversive odorant stimulus, and this has
been associated with subjective perceived
aversiveness.
 Olfactory System
• Olfaction is tightly associated with sexual
and reproductive responses.
• The structures of higher olfactory
processing in phylogenetically more
primitive animals have evolved in humans
into the limbic system, the center of the
emotional brain and the gate through which
experience is admitted into memory
according to emotional significance.
 Gustatory
• Discriminate only broad classes of stimuli
• Detection and discrimination of foods
involve a combination of other senses
 Autonomic Sensory System
Unconscious monitoring of basic functions
necessary for life: visceral organ activity,
blood pressure, cardiac output, blood
glucose levels, body temperature
 Motor Systems

• Basal Ganglia

• Cerebellum

• Motor Cortex
Basal Ganglia and Cerebellum
• The basal ganglia and cerebellum are large collections of
nuclei that modify movement on a minute-to-minute basis.
• Motor cortex sends information to both, and both
structures send information right back to cortex via the
thalamus.
• The output of the cerebellum is excitatory, while the basal
ganglia are inhibitory.
• The balance between these two systems allows for smooth,
coordinated movement, and a disturbance in either system
will show up as movement disorders.
Basal ganglia
 Basal Ganglia
• a collection of nuclei deep to the white
matter of cerebral cortex.
• The name includes: caudate, putamen,
nucleus accumbens, globus pallidus,
substantia nigra, subthalamic nucleus,
and historically the claustrum and the
amygdala.
Basal Ganglia functions and connections
• The caudate and putamen receive most of the input from
cerebral cortex; in this sense they are the doorway into the
basal ganglia.
• There are some regional differences: for example, medial
caudate and nucleus accumbens receive their input from
frontal cortex and limbic areas, and are implicated more in
thinking and schizophrenia than in moving and motion
disorders.
• The caudate and putamen are reciprocally interconnected
with the substantia nigra, but send most of their output to
the globus pallidus
Basal Ganglia functions and connections

The substantia nigra can be divided into two parts:

– substantia nigra pars compacta (SNpc)

– substantia nigra pars reticulata (SNpr)

– The SNpc receives input from the caudate and putamen,

and sends information right back. The SNpr also
receives input from the caudate and putamen, but sends
it outside the basal ganglia to control head and eye
movements.
– The SNpc is the more famous of the two, as it produces
dopamine, which is critical for normal movement.
– The SNpc degenerates in Parkinson's disease.
Basal Ganglia functions and connections
The globus pallidus can also be divided into two parts:
– globus pallidus externa (GPe)
– globus pallidus interna (GPi)

– Both receive input from the caudate and putamen, and both
are in communication with the subthalamic nucleus.
– It is the GPi, however, that sends the major inhibitory
output from the basal ganglia back to thalamus.
– The GPi also sends a few projections to an area of midbrain
(the PPPA), presumably to assist in postural control.
 Basal Ganglia
• Principal neurotransmitters: ACh, GABA, and
dopamine
• the overall effect on thalamus is inhibitory
• The function of the basal ganglia is often
described in terms of a "brake hypothesis"
• To sit still, you must put the brakes on all
movements except those reflexes that maintain an
upright posture.
• To move, you must apply a brake to some postural
reflexes, and release the brake on voluntary
movement.
 Basal Ganglia
• In such a complicated system, it is apparent
that small disturbances can throw the whole
system out of whack, often in unpredictable
ways.
• The deficits tend to fall into one of two
categories:
– the presence of extraneous unwanted
movements or
– an absence or difficulty with intended
movements.
 Lesions of the Basal Ganglia
• Parkinson's disease: the slow and steady loss of
dopaminergic neurons in SNpc.
• The three symptoms usually associated with
Parkinson's are tremor, rigidity, and
bradykinesia.
• The tremor is most apparent at rest.
• Rigidity is a result of simultaneous contraction of
flexors and extensors, which tends to lock up the
limbs.
• Bradykinesia, or "slow movement", is a difficulty
initiating voluntary movement, as though the brake
cannot be released.
 Lesions of the Basal Ganglia
• Huntington's disease, or chorea, is a hereditary
disease of unwanted movements.
• It results from degeneration of the caudate and
putamen, and produces continuous dance-like
movements of the face and limbs.
• A related disorder is hemiballismus, flailing
movements of one arm and leg, which is caused
by damage (i.e., stroke) of the subthalamic
nucleus.
Cerebellum
Inputs and Outputs of the Cerebellum
The cerebellum operates in 3's:

3) there are 3 highways leading in and out of the

cerebellum: the peduncles or stalks

5) there are 3 main inputs

7) and there are 3 main outputs from 3 deep nuclei

Inputs and Outputs of the Cerebellum

2) there are 3 highways leading in and out of

the cerebellum: the peduncles or stalks

1) inferior
2) middle
3) superior
Inputs and Outputs of the Cerebellum
there are 3 main inputs

• mossy fibers from the spinocerebellar pathways

• climbing fibers from the inferior olive
• more mossy fibers from the pons, which are carrying information
from cerebral cortex

• The mossy fibers from the spinal cord have come up ipsilaterally
• The fibers coming down from cerebral cortex, however, DO need to
cross (the cerebrum is concerned with the opposite side of the body,
unlike the cerebellum).
• These fibers synapse in the pons (hence the huge block of fibers in the
cerebral peduncles labeled "corticopontine"), cross, and enter the
cerebellum as mossy fibers.
Inputs and Outputs of the Cerebellum
The 3 deep nuclei are:

• Fastigial - primarily concerned with balance, and sends

information mainly to vestibular and reticular nuclei

• Interposed

• Dentate

The dentate and interposed nuclei are concerned more

with voluntary movement, and send axons mainly to
thalamus and the red nucleus.
 Cerebellum
• The cerebellum is involved in the coordination of
movement.
• it compares what you thought you were going to do
(according to motor cortex) with what is actually
happening down in the limbs (according to proprioceptive
feedback), and corrects the movement if there is a
problem.
• The cerebellum is also partly responsible for motor
learning e.g. riding a bicycle.
• Unlike the cerebrum, which works entirely on a
contralateral basis, the cerebellum works ipsilaterally.
Primary
Motor
System
 Basic Motor Pathway
• The motor pathways are pathways which originate
in the brain or brainstem and descend down the
spinal cord to control the a-motor neurons.
• These large neurons in the ventral horns of the
spinal cord send their axons out via the spinal
roots and directly control the muscles.
• The motor pathways can control posture, reflexes,
and muscle tone, as well as the conscious
voluntary movements that we think of when we
hear "motor system".
 Basic Motor Pathway
• The most famous pathway is the so called
"pyramidal system", which begins with the large
pyramidal neurons of the motor cortex, travels
through the pyramids of the brainstem, and finally
ends on or near the a-motor neurons.
• This system is extremely important clinically, as
strokes often affect the motor system. Therefore it
is crucial to understand the anatomy of the motor
pathway.
 Apraxia
Three levels:

• Limb-kinetic:
– inability to use the contralateral hand
• Ideomotor:
– inability to perform an isolated motor act upon
command
• Ideational:
– inability to perform in organized sequence a series of
skilled acts
 Motor
System
Pathway
 Autonomic Motor System
Parasympathetic: “deactivating”
Sympathetic: activating = fight or flight

Hypothalamus: controls appetite, rage,

temperature, blood pressure, perspiration,
sexual drive
Association Systems
 Basic Brain Organization
• Brainstem and reticular activating system: arousal
and attention
• Posterior cortex: perception and language
• Frontal cortex: generates programs and executes
plans; determines how the brain acts on its
knowledge
• Korbinian Brodmann: 47 distinct cytoarchitectural
areas
• Pierre Broca and Karl Wernicke: function
localization mapping
• DOMINANT and NON DOMINANT hemispheres:

Dominant Hemisphere process information in a

sequential, analytic, linear fashion, and efficient at
processing language and other symbolic information

Non Dominant Hemisphere- process information in

a gestalt , holistic, parallel fashion, and is
particularly efficient in processing visuospatial
information., unconscious processing, Prosody
 Language
Three-level processing in language comprehension:
2. Phonological processing (inferior gyrus of
frontal lobes)
3. Lexical processing (left temporal lobe)
4. Semantic processing (middle and superior gyri
of left temporal lobe)

Mirror pathways on both hemisphere:

Right = pure language skills
Left = prosody
Limbic System
• Papez believed that the experience of emotion was
primarily determined by the cingulate cortex and,
secondly, by other cortical areas.
• Emotional expression was thought to be governed
by the hypothalamus.
• The cingulate gyrus projects to the hippocampus,
and the hippocampus projects to the hypothalamus
by way of the bundle of axons called fornix.
• Hypothalamic impulses reach the cortex via relay
in the anterior thlamic nuclei.
• Emotion is not a function of any specific brain
center but of a circuit that involves four basic
structures, interconnected through several nervous
bundles : the hypothalamus with its mamillary
bodies, the anterior thalamic nucleus, the cingulate
gyrus and the hippocampus.
• This circuit (Papez circuit), acting in an harmonic
fashion, is responsible for the central functions of
emotion (affect), as well as for its peripheral
expressions (symptoms).
• More recently, Paul McLean, accepting the
essential bases of Papez proposal, created the
denomination limbic system and added new
structures to circuit : the orbitofrontal and
medialfrontal cortices (prefrontal area), the
parahippocampal gyrus and important subcortical
groupings like the amygdala, the medial thalamic
nucleus, the septal area, prosencephalic basal
nuclei (the most anterior area of the brain) and a
few brainstem formations.
Limbic System

Structures:
Amygdala
Cingulate Gyrus
Fornix
Hippocampus
Hypothalamus
Olfactory Cortex
Thalamus
 Amygdala

• If you remember only one word about the

amygdala, the word is FEAR.
• The amygdala is the nucleus responsible for the
lurch you feel in your stomach when you turn
around in a dark alley and notice someone
following you.
• It couples a learned sensory stimulus (man in ski
mask in alley = danger) to an adaptive response
(fight or flight).
 Amygdala
• Inputs:

the amygdala must get sensory input, and it

must be fairly highly processed input to
recognize the elements of a scene that
signal danger. The association areas of
visual, auditory, and somatosensory cortices
are the main inputs to the amygdala.
 Amygdala
• Outputs:

the amygdala must be able to control the

autonomic system, to provoke such an
instant sympathetic response. The main
outputs of the amygdala are to the
hypothalamus and brainstem autonomic
centers, including the vagal nuclei and the
sympathetic neurons.
 Amygdala
• The amygdala is also involved with mood
and the conscious emotional response to an
event, whether positive or negative. To this
end, the amygdala is also extensively
interconnected with frontal cortex,
mediodorsal thalamus, and the medial
striatum.
 Memory
• There are at least three different types of memory.
• The most short term is working memory.
• Working memory is like the RAM of a computer. It is the
type of memory that enables you to spit back the last
sentence of a conversation when someone accuses you of
not listening.
• Like the RAM of a computer, it is crucial for performing
some common operations in your head: adding numbers,
composing a sentence, following directions, etc.
• Also like a computer, the space devoted to that operation is
recycled as soon as you turn to something else.
• It does not become a permanent memory.
• Working memory does not require the hippocampus; it is
probably a cortical phenomenon.
 Hippocampus and Memory
• The second type is what we most commonly
associate with "memory".
• This is long-term or declarative memory, and is
composed of all the facts, figures, and names you
have ever learned.
• All of your experiences and conscious memory
fall into this category.
• It is analogous to the hard drive of a computer.
• Although no one knows exactly where this
enormous database is stored, it is clear that the
hippocampus is necessary to file away new
memories as they occur.
 Hippocampus and Memory
• The third type is procedural memory, and is
probably the most durable form of memory.
• These are actions, habits, or skills that are learned
simply by repetition.
• Examples include playing tennis, playing an
instrument, solving a puzzle, etc.
• The hippocampus is not involved in procedural
memory, but it is likely that the cerebellum plays a
role in some instances.
 Hippocampus and Memory

• Therefore, the hippocampus is critical in laying

down declarative memory, but is not necessary for
working memory, procedural memory, or memory
storage.

• Damage to the hippocampus will only affect the

formation of new declarative memories.
Prefrontal Area
 Prefrontal Area
• This area comprises the entire non-motor anterior region of
the frontal lobe.
• It underwent a great deal of development during the
evolution of mammals.
• It is specially large in man and in some species of
dolphins.
• It does not belong to the traditional limbic circuit, but its
intense bi-directional connections with thalamus,
amygdala and other subcortical structures, account for the
important role it plays in the genesis and, specially, in the
expression of affective states.
 Prefrontal Area
• When the pre-frontal cortex suffers a lesion, the subject
looses his sense of social responsibility as well as the
capacity for concentration and abstraction. In some cases,
although consciousness and some cognitive functions, like
speech, remain intact, the subject can no longer solve
problems, even the most elementary ones.
• When pre-frontal lobotomy was used for treatment of
certain psychiatric disturbances, the patients entered into a
stage of "affective buffer", no longer showing any sign of
joy, sadness, hope or despair.
• In their words or attitudes, no traces of affection could be
detected.
 Psychiatric Implications
• Four A of schizophrenia = brain functions
subserved in part by limbic structures
• Reduced gray matter volume (hippocampus,
amygdala, parahippocampus)
• Decreased frontal lobe activation
• Activation of the same areas for spoken language
as that in auditory hallucination
• Frontal lobe injury impairs executieve functions:
motivation, attention, sequencing of actions
 Psychiatric Implications
• Frontal lobe injury impairs executive
functions: motivation, attention, sequencing
of actions
• frontal lobe syndrome: slowed thinking,
poor judgment, decreased curiosity, social
withdrawal, irritability
 Neural Development
• Migration to adult sites
• Heterotopia (incorrectly placed neurons)
• Auditory processing and language:
– Temporally determined perceptual map of phonemes
– Nueronal location of specific sounds differ across cultures
(difficulty of Japanese to distinguish “la” from “ra”)
– Very early experiences may establish the density and
fidelity of neural circuits for specific functions
 Psychiatric Implications
• nature and nurture
• Milieu affects neural development such that a person may
either be:
– given an advantage (e.g. musically exposed being better at
mathematics and spatial reasoning)
– or disadvantaged (e.g. pattern of trauma or fear flood amygdala to
be specifically alert to threatening stimuli; or chaos for poor
acquisition of complex cognitive skills later)

• Tantalizing basis for development theories

• Early experiences primes the basic circuitry for language,
emotion, and other advanced behaviours
Neurophysiology and
Neurochemistry
 Synaptic Transmission
• Synaptic transmission = propagation of nerve impulses from one nerve
cell to another.
• Neurotransmitter release into synaptic space = nerve impulses
transmission
• Synapse = junction at which the axon of the presynaptic neuron
terminates at some location upon the postsynaptic neuron.
• Terminal button = enlarged structure at end of a presynaptic axon,
where it is juxtaposed to the postsynaptic neuron
• An axon can make contact anywhere along the second neuron:
– on the dendrites (an axodendritic synapse)
– on the cell body (an axosomatic synapse)
– on the axons (an axo-axonal synapse).
 Synaptic Transmission
• The neurotransmitters are a diverse group of
chemical compounds ranging from simple amines
such as dopamine and amino acids such as
gaminobutyrate (GABA), to polypeptides such as
the enkephalins.
• The mechanisms by which they elicit responses in
both presynaptic and postsynaptic neurons are as
diverse as the mechanisms employed by growth
factor and cytokine receptors.
 Presynaptic Components
• voltage gated calcium channels locally raise intracellular
Ca concentration and initiates cascade of interaction
• neurotransmitter containing vesicles fuse with the
presynaptic membrane and undergoes exocytosis
• neurotransmitter diffuse into cleft and binds to specific
receptors on external membrane of the postsynaptic
neuron.
• Tansmembrane transporter molecules return free Mono
Amine NT to nerve terminals where they are repackaged
into vesicles for release or degraded by MAO.
(Mao type A metabolize Norepinephrine and Serotonin and its inhibition by Mao
inhibitors is associated with mood elevation. Mao B metabolize Dopamine)
 Postsynaptic Components
 

Receptors are the site of action of most available psychoactive

substances.

Principal functions of these receptors- to alter electrical

transmembrane potential to either increase or decrease
likelihood of triggering an action potential

Sensitivity of receptors are due to

a. number of receptors present
b. affinity of the receptor for the neurotransmitter
c. efficiency of translation of both neurotransmitter
and receptor into a neuronal message
 Postsynaptic Components
 

• G Proteins
• Second Messengers
– Cyclic Nucleotides
– Calcium
– Phosphoinositol Metabolites
– Eicosanoids
– JAK-STAT
• Protein Kinases
 Neurotransmitter Receptors
• Once the molecules of neurotransmitter are released from a
cell as the result of the firing of an action potential, they
bind to specific receptors on the surface of the
postsynaptic cell.
• In all cases in which these receptors have been cloned and
characterized in detail, it has been shown that there are
numerous subtypes of receptor for any given
neurotransmitter.
• As well as being present on the surfaces of postsynaptic
neurons, neurotransmitter receptors are found on
presynaptic neurons.
• In general, presynaptic neuron receptors act to inhibit
further release of neurotransmitter.
 Neurotransmitter Receptors
• The vast majority of neurotransmitter receptors belong to a
class of proteins known as the serpentine receptors.
• This class exhibits a characteristic transmembrane structure:
that is, it spans the cell membrane, not once but seven times.
• The link between neurotransmitters and intracellular
signaling is carried out by association either with G-proteins
(small GTP-binding and hydrolyzing proteins) or with
protein kinases, or by the receptor itself in the form of a
ligand-gated ion channel (for example, the acetylcholine
receptor).
• One additional characteristic of neurotransmitter receptors
is that they are subject to ligand-induced desensitization:
That is, they can become unresponsive upon prolonged
exposure to their neurotransmitter.
 Neurotransmitters
• 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 neuron or the synaptic
cleft acts to remove or deactivate the
neurotransmitter
 Transmitter Molecule Derived From Site of Synthesis

Acetylcholine Choline CNS, parasympathetic nerves

Serotonin
Tryptophan CNS, chromaffin cells of the gut, enteric cells
5-Hydroxytryptamine (5-HT)

GABA Glutamate CNS

Glutamate   CNS
Aspartate   CNS
Glycine   spinal cord

Histamine Histidine hypothalamus

Epinephrine
Tyrosine adrenal medulla, some CNS cells
synthesis pathway

Norpinephrine
Tyrosine CNS, sympathetic nerves
synthesis pathway

Dopamine
Tyrosine CNS
synthesis pathway

Adenosine ATP CNS, periperal nerves

ATP   sympathetic, sensory and enteric nerves

Nitric oxide, NO Arginine CNS, gastrointestinal tract

Metabolism of Catecholamine
Neurotransmitters
Dopaminergic
pathway
• The first is the mesolimbic pathway–the bundle of
dopaminergic fibres associated with the reward
circuit.
• This pathway originates in the ventral tegmental
area and innervates several structures of the
limbic system, including the nucleus accumbens.
• The mesolimbic pathway is important for memory
and for motivating behaviours.
• By blocking this pathway, antipsychotic drugs
reduce the intense emotions caused by conditions
such as schizophrenia.
• The mesocortical pathway also originates in the
ventral tegmental area, but projects to the frontal
cortex and surrounding structures.
• Some evidence indicates that a malfunction in this
pathway might be the cause of some of the
symptoms of schizophrenia, such as hallucinations
and disordered thinking.
• Medications that block this pathway reduce
psychotic delirium, but also reduce the overall
activity of the frontal lobes.
• The third, nigrostriatal pathway projects
axons from the substantia nigra to the
striatum (caudate nucleus and putamen),
which is involved in motor control.
Degeneration of the neurons in this pathway
is associated with the trembling and
muscular rigidity symptomatic of
Parkinson’s disease.
• A fourth dopaminergic pathway worth
mentioning is the tuberoinfundibular
pathway, which connects the hypothalamus
to the pituitary gland, where it influences
the secretion of hormones such as prolactin.
 Serotonin
• naturally produced in the Pineal gland
which lies deep at the centre of the human
brain.
• The average adult human possesses only 5
to 10 mg of serotonin, 90 % of which is in
the intestine and the rest in blood platelets
and the brain.
 Involved in the control of
• Appetite
• Sleep
• memory and learning
• temperature regulation
• Mood
• Behaviour
• cardiovascular function
• muscle contraction
• endocrine regulation
• depression
 GABA
• Several amino acids have distinct excitatory or
inhibitory effects upon the nervous system. The
amino acid derivative, g-aminobutyrate, also
called 4-aminobutyrate, (GABA) is a well-known
inhibitor of presynaptic transmission in the CNS,
and also in the retina. The formation of GABA
occurs by the decarboxylation of glutamate
catalyzed by glutamate decarboxylase (GAD).
GAD is present in many nerve endings of the
brain as well as in the b-cells of the pancreas.
Neurons that secrete GABA are termed
GABAergic.
 GABA
• GABA exerts its effects by binding to two distinct
receptors, GABA-A and GABA-B. The GABA-A
receptors form a Cl- channel. The binding of
GABA to GABA-A receptors increases the Cl-
conductance of presynaptic neurons. The
anxiolytic drugs of the benzodiazepine family
exert their soothing effects by potentiating the
responses of GABA-A receptors to GABA
binding. The GABA-B receptors are coupled to an
intracellular G-protein and act by increasing
conductance of an associated K+ channel.
Monoamine neurotransamitters

• present in only a small percentage of neurons

localized in small nuclei of the brain

• have enormous impact on total brain functioning

because the diffuse projections of axons from these
monoaminergic neurons can affect virtually every
brain region.
  

Amino Acids
• Most abundant neurotransmitter   
1.  GaBa – major inhibitory N. ( Bzd act on 
this mechanism)  
2.  Glutamate- major excitatory N.  NMDA is 
the most understood receptor of glutamate 
and has a role in learning memory and 
psychopathology  : 
psychosis , Schizophrenia
• and it is possible to conceptualize the brain
as reflecting the balance between the
excitatory amino acid glutamate, and the
inhibitory amino acid g-aminobutyric acid
• all existing drugs for psychiatric conditions
act through monoamine or amino acid
neurotransmitter systems
 Peptides
• A.       Endogenous opiods- 
    1.  involved in regulation of stress, pain, mood
    2.  Endogenous opiods :
            enkephalins, endorphins, dynorphins
    3. effects of neurotransmission in  hippocampus:    
           contributes to addiction
B.       Substance P
     1. Primary neurotransmitter in sensory neurons &  
         strianigral pathway; associated with mediation   
         of pain
C.       Cholecystokinin
      involved in pathophysiology of Schizophrenia, 
      eating and  movement disorders
Somatostatin

   1. growth hormone inhibiting factor
   2. implicated in Huntington’s disease, Alzheimer’s   
dementia
 
Vasopressin and Oxytoxin

   1. synthesized in the hypothalamus
   2. mood regulation
 
Neuropeptide Y

  1.  stimulate appetite
  2.  area of interst in Obesity
 Nucleotides 

Purine adenosine inhibits the release of other 
neurotransmitters  and ATP
 
Gasses 

     Nitric Oxide  acts as both intraneuronal second 
messenger and neurotransmitter.  With  excessive 
exposure to glutamate Nitric  Oxide  is metabolized to 
toxic free radicals which may injure or kill  cells 
through excitotoxicity
 
Eicosanoids
Anandamides            
Sigma receptors
 Neurotrophic factors
• Growth factors that allow neurons to regenerate their axon
are also called neurotrophic factors. NGF (Nerve Growth
Factor) is the most widely-known. Recently, other factors
have been identified, such as BDNF (Brain-Derived
Neurotrophic Factor), CNTF (Ciliary Neurotrophic
Factor), GDNF (Glial Cell-line Neurotrophic Factor), and
IGF (Insulin Growth Factor), to name only a few.
 Neurotransmitters:
• Neurons can also be classified according to the
neurotransmitters they contain (e.g., the dopamine neurons
of the substantia nigra).

• neurotransmitters have defined effects on the activity of

neurons, whereas complex brain functions, such as those
disturbed in psychiatric disorders, are mediated by the
coordinated activity of ensembles of neurons.

• effects of neurotransmitters on behavioral, emotional, or

cognitive states must be viewed within the context of the
neural circuits that they influence.
Genetics and Brain Development

Alterations in gene expression occur both

during development and in adulthood and
may be the bases for abnormal and normal
development, and for abnormal and normal
adaptation to stress
The normal affective, cognitive, and behavioral
processes that are disturbed in different psychiatric
disorders arise because of specific patterns of
activation in networks of neurons that are distributed
through the central nervous system. These patterns of
activation are mediated by the connections among
specific brain structures.
• Every function of the human brain is a consequence of the
activity of specific neural circuits. The circuits form as a
result of several developmental processes

• In early development, some axons initially produce an

excessive number of axon branches or collaterals and thus
contact a broader set of targets than are present in the adult
brain

• During later development the connections of particular

neurons are focused by the pruning or elimination of
axonal projections to inappropriate targets.
• the role of any particular brain region or group of
neurons in the production of specific behaviors or in
the pathophysiology of a given neuropsychiatric
disorder but must be considered within the context of
the neural circuits connecting those neurons with other
brain regions.

Illnesses in the Brain cannot be 
viewed in isolation
 Population Genetics
provided some of the first objective data that mental
illnesses were biological illnesses, thereby helping to
destigmatize these human conditions

application of molecular neurobiological tools led to

the ability to study specific genetic linkages among
individuals and groups of individuals

application lead to the identification of a specific gene

or genes as causative agents for specific mental
disorders.
 Psychoneuroendocrinology
• Endocrine disorders are frequently
associated with secondary psychiatric
symptoms (e.g. depression)
• A significant percentage of patients
suffering from psychiatric syndromes
display regular patterns of endocrine
dysfunction
• The interactions between the neuroendocrine and
central nervous systems :

3. psychiatric symptoms that accompany some

hormonal disorders (e.g., depression in Cushing's
syndrome)
4. In the identification of disorders wherein
neuroendocrine regulation is utilized as potential
markers for state or trait variables in psychiatric
conditions
• Pathological alterations in
hypothalamic-pituitary-adrenal
function have been associated with
mood disorders, posttraumatic stress
disroder, Alzheimer’s dementia,
substance use disorders
• Insulin: depression common in DM
• Hypothalamic-pituitary-gonadal axis

– Testosterone: increased violence and

aggression, mood improvement, sexual
desire
– Estrogen: mood enhancement
– Increased Prolactin: depression,
decreased libido, stress intolerance,
anxiety, increased irritability
• Hypothalamic-pituitary-thyroid axis

– Neuronal excitability, behaviour,

neurotransmitter regulation
– Hyperthyroidism: fatigue, irritability, insomnia,
anxiety, restlessness, weight loss, emotional
lability, impairment in concentration and
memory
– Hypothyroidism: fatigue, decreased libido,
memory impairment, irritability, suicidal
ideation
 Psychoneuroimmunology
• Classical conditioning paradigms have been
associated with suppression or enhancement
of the immune response
• Stressful life events can increase
susceptibility to infectious diseases
• Academic/examination stress in medical
students showed decreased natural killer cell
activity, T cells, mitogen responses,
interferon production, impaired cellular
immunity
 Psychoneuroimmunology
• Altered CNS function results from a
combination of the direct effects of an
injurious event on vaiorus cell types and the
effects of inflammatory mediators on
neurons and supporting cells
• Involvement of viral infection during neural
development in some cases of schizophrenia
• Immune activation may contribute to the
pathophysiology of depression
 Biological Rhythms and
Chronobiology
• circadian rhythms are set by zeitgebers
principally emanating from pontine
reticular formation and
suprachiasmatic nuclei of the
hypothalamus
• Phase advance or phase delay
• Depression is the most commonly
associated symptom in biological
rhythm disruption
 Conclusion
• understanding the neurobiological bases for
psychiatric disorders requires an
appreciation of the major principles
governing the functional organization and
connections in the human brain.