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ñ Various receptor nerve terminals act in

 !"#j#$%&#'"(#j% ("##!")* concert to mediate distinct modalities.
ñ Nerve endings are either fast or slow
%('" ++*+!%) ñ After sensory fibers enter the spinal cord,
ñ Sensory Systems they are sorted into one of the three fiber
p Create an internal representation of the tracts:
external world. p Some fibers travel locally and
p A separate map is formed for each sensory synapse within   -   
modality.   . These projections
ñ Motor Systems participate in further filtering of the
p Enable persons to manipulate their sensory input by suppressing
environment and to influence other¶s unwanted ³noise´ to allow sharper
behavior through communication. delineation of the signal
ñ Association (Association Unit) p Fibers for conscious perception of
p Unit in the brain wherein sensory input, touch, pain and temperature
representing the external world, is integrated decussate at the level of entry into
with internal drivers and emotional stimuli. the spinal cord and

+%+"(*+*+!%)+
ñ Must both detect and discriminate stimuli. ascend to the brain in the
ñ Feature extraction ± quintessential role of sensory  


systems. 1. j   

ñ First transform physical stimuli into neural activity in 
 ± localized, discrete,
the primary sense organs and then refine and narrow acute pains.
the neural activity in a series of higher cortical 2. )
  

processing areas. 
 ± along with
ñ Neural processing ± eliminates irrelevant date from spinoreticulothalamic
higher representations and reinforces crucial features. pathway: diffuse, chronic
ñ Highest Levels of sensory processing ± neural images pains.
p Fibers for conscious perception of
are transmitted to the association areas to be acted
touch, vibration sense and
on in the light of emotions and drives.
proprioception in the    
ñ Two Paradigm for all sensory systems:

 , without immediate
1. Nature and Nurture
decussation.
ñ Genetics and experience
ñ All somatosensory fibers project to, and
ñ Suggested an innate, genetically determined
synapse in, the thalamus. The thalamic
mechanism of synaptic pattern formation neurons preserve the somatotopic
2. Highly specialized brain cells that respond representation by projecting fibers to the
exclusively to extremely specific stimuli. somatosensory cortex, located immediately
ñ ³Grandmother cell´ ± a cell that would fire posterior to the sylvian fissure in the parietal
only when a subject was regarding his or her lobe (Brodmann areas 1,2,3)
own grandmother. ñ Within each band is the sensory homunculus
ñ Tactile agnosia or Astereognosis is defined
!  +  
by the inability to recognize objects based on
, +    + 
touch although he primary somatosensory
ñ An intricate array of parallel point-to-point
modalities are intact.
connections from the body surface to the
ñ Primary somatosensory modalities:
brain.
p Light touch
ñ First sensory system understood in
p Pressure
anatomical detail. p Vibration
ñ 6 somatosensory modalities: p Proprioception
p Light Touch ñ Strict somatotropic representation exists at
p Pressure each level of the somatosensory system.
p Pain Neurons extend axons to connect to distant
p Temperature brain regions and a set of axons must
p Vibration therefore sort itself to preserve the
p Proprioception (position sense) somatotropic organization.
ñ Somatotopic ± the organization of nerve
ñ In adults, the classic mapping studies of
bundles and synaptic connections in the r
  . 
suggested the existence of
somatosensory system encodes spatial a  
 - an immutable corticacl
relationships at all levels. representation of the body surface.

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 ñ More recent experimental evidence has cues, with preservation association areas
promoted a more plastic conception than of other sensory
Penfield¶s; i.e , shifts in the map occur in modalities
response to loss of cortex form stroke and Associative Inability to name or use Bilateral medial
injury. Visual Agnosia objects despite the occipitotemporal
ñ The cortical map can be rearranged solely in ability to draw them lesions
response to a change in the pattern of tactile Color Agnosia Inability to recognize Dominant
stimulation of the fingers. color despite being able occipatl lobe
ñ Internal representation of the external world, to match it lesions that
while static in gross structure, may be Color Anomia Inability to name a color include splenium
continuously modified at the level of synaptic despite being able to of corpus
connectivity to reflect relevant sensory point it. callosum
experiences. Central Complete inability to
ñ Cortical representations of sensory input or Achromatopsia perceive color
of memories may be holographic rather than Anton¶s Failure to acknowledge Bilateral occipital
spatially fixed; the pattern of activity, rather Syndrome blindness, possibly lobe lesions
than the physical structure, may encode owing to interruption of
information. fibers involved in self-
Ñ, '+  assessment
ñ Visual images are transduced into neural Balint¶s Triad: Bilateral Parito-
activity within the retina ad are processed Syndrome Optic Ataxia (inability to occipital lesions
through a series of brains cells, which direct optically guided
respond to increasingly complex features movements);
from the eye to the higher visual cortex. Oculomotor Apraxia
ñ Visual Pathway: (inability to direct gaze
p Optic disk (retina) * optic nerve * rapidly);
optic chiasm * optic tracts * Lateral Simultanagnosia
Geniculate Nucleus (Body) * visual (inability to integrate a
cortex visual scene to perceive
p (  ± Rods and Cones it as a whole)
A (
/intesnisty of light Gerstmann Includes: Dominant
A   ± 3 types, respond Syndrome Agraphia, Acalculia, parietal lobe
most strongly to one of the Right-Left disorientation lesions
3 primary colors. and Finger agnosia.
p   0 
     /
stimulating a point immediately 3, #
 + 
suppresses the response of circle ñ Sounds are instantaneous, incremental
of neighboring cells. changes in ambient air pressure.
ñ  '   1 ± respond ñ Pathway:
specifically to   .  
.
 p Pressure change * vibration *
  . The cells of primary visual ossicles * endolymph (cochlear
cortex projects to Secondary Visual Cortex spiral) * cilia movement (hair cells)
ñ +

 '   1 ± respond * generate neural impulses *
specifically to 
     . cochlear nerve * cochlear nuclei *
 
   , Lateral Lemniscus (Inferior colliculi)
ñ  .   !   j  ± detects the * Medial Geniculate Nucleus/Body
  .  

  .   2
. The (Thalamus) * Primary auditory
WHAT questions. cortex (Posterior Temporal Lobe)
ñ     !   j  ± tracks   ñ j 1
 
  - the extraction of

     


. The vowels, consonants and words from the
WHERE question auditory input, occurs in higher language
ñ  .  !   
! association areas in the left temporal lobe.
p j .! ± facial features
p (! ± complex shapes
ñ "

 

  are stripes of Word Characterized by intact Damage to the
cortex that receive input from only one eye, Deafness hearing for voices but an left parietal
separated by stripes innervated only by inability to recognize cortex;
fibers for the other eye. speech Disconnection of
the auditory
 

  cortex from
Prosopagnosia Inability to recognize Disconnection of Wernicke¶s area
faces Left ITC from the Auditory Inability to recognize Right
visual Sound nonverbal sounds, in the hemisphere
association area Agnosia presence of intact correlate of pure
in the left parietal hearing and speech word deafness
lobe recognition
Apperceptive Inability to identify and Bilateral lesions  

 
Visual Agnosia draw items using visual in visual 

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o, ".

 p Modulation of motor acts
ñ Odorants, or volatile chemical cues, enter
the nose, solubilized in the nasal mucus and
bind to odorant receptors displayed on the
surface of the sensory neurons of the
olfactory epithelium
ñ Each neuron in the epithelium displays a
unique odorant receptor.
ñ Humans possess several hundred distinct
receptor molecules that bind the huge variety
of environmental odorants.
ñ The most ancient sense in evolutionary
terms
ñ Tightly associated with sexual and
reproductive responses.
ñ Pathway:
p Binding of odorant/s * neural


impulse * sensory nerves along
cribriform plate * olfactory bulb *
glomeruli * Olfactory Cortex
ñ Olfactory signals do not pass through the
thalamus.
ñ ' 

 "  is thought to detect disease and carbon monoxide poisoning.
pheromones.
 and flapping movements of arms
4, ! 
ñ Sense of taste is believed to discriminate
only broad classes of stimuli: sweet, sour,
bitter and salty.
ñ Each modality is mediated through a unique
set of cellular receptors and channels.
ñ Pathway:
p Soluble chemical binding to mouth
receptors * stimulation of gustatory
nerves * nucleus solitaries of
brainstem
)"!"(+*+!%)+
ñ The movements of the body muscles are controlled
by the lower motor neurons.
ñ The firing motor neurons are regulated by the
summation of upper motor neuron activity.
ñ Primitive systems produce gross coordination
movements of the entire body
p Activation of the rubrospinal tract stimulates
flexion of all limbs whereas activation of the
vestibulospinal tract causes all limbs to
extend.
ñ Coticospinal tract is at the top of the motor hierarchy
p Controls fine movements and which
eventually dominates the brainstem system
during the first years of life.
p Upper motor neurons of CST is at the


 1
posterior frontal lobe known as motor strip or
brodmann area 4.
5 
ñ A subcortical group of gray matter nuclei

# 
ñ Mediate postural tone
ñ Four functionally distinct ganglia:
p Striatum
p Pallidum
p Substantia nigra
p Subthalamic nucleus

ñ Collectively known as the Corpus Striatum, Caudate
and Putamen.
ñ 
p Gatekeeper to allow the motor system to
perform only those acts that are goal
directed.
p Failure to perform as gatekeeper: 
A Obsessive-compulsive disorder
A Tic disorders such as Tourette¶s
disorder
p Overactivity of the striatum owing to lack of
dopaminergic inhibition results in
bradykinesia.
p Huntington¶s disease
A Caudate shrinks dramatically
A Characterized by rigidity
superimposed by choreiform
p Thought to influence associative or cognitive
processes
ñ 5
p Internal or external parts
p Nested within the concavity of the putamen
p Receives input from the corpus striatum and
projects fibers to the thalamus
p May be severely damaged in Wilson¶s
A Characterized by dystonic posturing
and legs.
ñ + 
p The black substance because of the
presence of melanin pigment
p Parkinsons¶ disease
A Characterized by rigidity and tremor
associated with depression
ñ +

 
p Yield ballistic movements, sudden limb jerks
or such velocity that they are compared to
projectile movement
ñ Together, initiating and maintaining the full range of
useful movements.
   
ñ Simple six-cell pattern of circuitry
ñ Activated several milliseconds before a planned
movement
ñ Ablation renders intentional movements coarse and
tremulous
ñ Carefully modulates the tone of agonistic and
antagonistic muscles by predicting the relative
contraction needed for smooth motion
ñ Prepared motor plan is used to ensure that exactly
the right amount of flexor and extensor stimuli is sent
to the muscles.
)
ñ Brodmann area 4, motor strip
ñ Somatotopic map of the motor neurons is found.
ñ Individual cells within the motor strip cause
contraction of single muscles.
ñ +  )
p Brodmann area 6
p Brain region immediately anterior to the
motor strip
p Contains cells that when individually
stimulated can trigger more complex
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 movements, by influencing a firing sequence
of motor strip cells 
" 7

.  
ñ Korbinian Brodmann
ñ 1 ± skillful use of the hands p 47 areas on the basis of cytoarchitectonic
ñ #1± deficits in skilled movements distinctions
p 3 levels: p Cataloguing that has been remarkably
A Limb-kinetic durable as the functional anatomy of the
A Ideomotor brain has been elucidated
A Ideational ñ Brainstem and Thalamic reticular activating system
p j06 
 provide arousal and set up attention
A Inability to use the contralateral ñ Posterior cortex integrates perceptions and generates
hand in the presence of preserved language
strength ñ Frontal cortex generates programs and executes
A Results from isolated lesions in the plans like an orchestra conductor
supplementary motor area ñ Hemispheric lateralization of function is a key feature
p 



#1 of higher cortical processing.
A Inability to perform an isolated ñ Primary sensory cortices for touch, vision, hearing,
motor act upon command despite smell and taste are represented bilaterally, however
preserved comprehension, the highest level of feature extraction are generally
strength, and spontaneous unified in one brain hemisphere only.
performance of the same act. p The clearest known example of hemispheric
A Simultaneously affects both limbs lateralization is the localization of language
and involves functions so functions to the left hemisphere. (Pierre
specialized that they are localized Broca and Karl Wernicke)
to only one hemisphere. ñ Prosody the emotiona and affective components of
A Disconnection of the language language, or body language, appears to be localized
comprehension area, Wernicke¶s in a mirror set of brain units in the right hemisphere
area, from the motor regions
causes inability to follow spoken
commands
A Lesions to the left premotor area
may impair the actual motor
program as it is generated by the
higher-order neurons.
p 

1
A when the individual components of
a sequence of skilled acts can be
performed in isolation, but the entire
series cannot be organized and
executed as a whole.

# 
)  + 

ñ  
 +  slows the heart rate and
begin the process of digestion
ñ + 
 +  mediated the fight or flight
response, increased heart rate, shunting of blood
away from the viscera, and increased respiration j
+ 
ñ &
 ± brain center that drives the ñ A circuit of phylogenetically ancient structures
autonomic motor system which houses a set of paired ñ Responsible for generating and modifying memories
nuclei that appear to control appetite, rage, and for assigning emotional weight to sensory and
temperature, blood pressure, perspiration, and sexual recalled experience
drive. ñ #
receives fibers from all sensory areas and
appears to serve as a gate for the assignment of
#++"#!"+*+!%)+ emotional significance to memories.
 ( . 1

ñ Primitive reflex arc may mediate the brisk withdrawal
of a limb from a painful stimulus, without immediate
conscious awareness
ñ Peripheral stimulation of sensory nerve which in turn
directly activates the motor neuron that drives the
muscle to contract
ñ This response is strictly local and all-or-none
ñ Rarely generate an organism¶s behaviors
ñ For behaviors, sensory systems project to association
areas where sensory information is interpreted in
terms of internally determined memories, motivations,
and drives.

‡ Localization of specific brain functions
‡ Arousal and Attention
‡ Arousal ± establishment and maintenance of an awake state.
Requires at least 3 brain regions:
ƕ brainstem: ascending reticular activating system
(ARAS) ± diffuse set of neurons appears to set the
level of consciousness.
ƕ Intralaminar nuclei of thalamus
ƕ cortex
‡ ARAS ĺ Intralaminar nuclei of the thalamus ĺ cortex
‡ thalamus and cortex: fire rhythmical burst of neuronal activity
at 20 to 40 cycles per second
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‡ sleep:burst are not synchronized
‡ wakefulness: ARAS stimulates thalamic intralaminar nuclei
which in turn coordinates the oscillations of different cortical
regions, greater synchronization means higher level of
wakefulness
‡ absence of arousal: stupor and coma
‡ produce stuporous state:
ƕ small discrete lesions of the ARAS
ƕ large bilateral lesions in the hemisperic level
‡ Maintenance of attention requires intact right frontal lobe
‡ Memory
‡ Immediate memory ± functions over a period of seconds
ƕ components:
ƒ phonological ± left hemisphere
ƒ visuospatial ± right hemisphere
ƕ working memory ± ability to store information for
several seconds, while other, related cognitive
operation take place on this information. It
incorporates immediate and recent memory.
Dorsolateral prefrontal cortex
‡ recent memory ± minutes to days
‡ remote memory ± months to years
Brain structures critical to formation of memories
ƕ medial temporal lobe ± houses the hippocampus ±
adjacent to amygdala: rates the emotional
importance of an experience and to activate the level
of hippocampal activity accordingly.
ƒ Hippocampal place code: a pattern of
cellular activation in the hippocampus that
corresponds to the animal's location in
space.
ƕ certain diencephalic nuclei
ƕ basal forebrain
‡ declarative or factual memory may be separate within the
brain
form procedural or skill related memory
‡ amygdala, afferent and efferent fiber tracts of the
hippocampus
± essential to the formation of memories
‡ left hippocampus ± more efficient at forming verbal memories
‡ right hippocampus ± form nonverbal memories
‡ memorized motor acts initially require activation of the medial
temporal lobe
‡ Corticalization of motor commands: practice ĺ larger
segments of an act necessary to achieve a goal become
encoded within discrete areas of the premotor and parietal
cortices (left parietal cortex) ĺ much more limited activation of
the cortex during highly skilled acts ± medial temporal lobe is
bypassed.
‡ Within the diencephalon ± dorsal medial nucleus and
mamillary bodies: necessary for memory formation
ƕ damaged in thiamine deficiency states ± korsakoff's
syndrome
ƕ korsakoff's syndrome: severe inability to form new
memories and a variable inability to to recall remote
memories
‡ alzheimer's disease: degeneration of neurons and their
replacement by senile plaques and neurofibrillary tangles.
ƕ Cognitive decline ± loss of synapses
ƕ Initially, parietal and temporal lobes are affected,
relative sparing of frontal lobes
ƕ early symptoms: loss of memory ± temporal lobe
function, impaired syntactical language
comprehension and visuospatial oranization ±
parietal lobe function
ƕ late symptoms: personality changes ± frontal lobe
functions

‡ Pick's disease: cortical degeneration syndrome, first affects
the
frontal lobe while sparing the temporal and parietal lobes.
There are early disinhibition and impaired language expression
(frontal dysfunction)
‡ memory loss can also result from disorders of the subcortical
gray matter structures (basal ganglia & brainstem nuclei),
diseases of the white matter or both.
Language:
‡ Broca's 1865: loss of fluent speech caused by a lesion in the
left inferior frontal lobe
‡ wernicke's 1874: localization of language comprehension to
the left superior temporal lobe
‡ language demonstrates hemispheric localization of function,
the hemisphere dominant for language also directs the
dominant hand.
‡ Innate tendency to lateralization of language in the left
hemisphere is highly associated with an asymmetry of the
planum temporale ± traingular cortical patch on the superior
surface of the temporal lobe, appears to harbor wernicke's
area.
‡ Mixed hemispheric dominance for language ± absence of the
expected asymmetry of the planum temporale
‡ language comprehension is processed in 3 levels:
ƕ phonological functioning ± individual sounds such as
vowels or consonants are recognizes in the inferior
gyrus of the frontal lobes, improves if:
ƒ lip reading is allowed
ƒ speech is slowed
ƒ contextual clues are provided
ƕ lexical processing ± matches the phonological input
with recognized words or sounds in the individual's
memory. Determines whether the sound is a word or
not. Left temporal lobe: representations of lexical
data are organized according to semantic category
ƕ semantic processing ± connects the words to their
meaning. Activates the middle and and superior gyri
of the left temporal lobe, whereas the representation
of the conceptual content of words is widely
distributed in the cortex
‡ language production: cortical semantic representations ĺ left
temporal lexical nodes ĺ oromotor phonological processing
area (speech) or graphomotor system (writing)
‡ perception of prosody and appreciation of ³body language´
requires an intact right hemisphere
‡ developmental dyslexia: unexpected difficulty in learning in
the
context of adequate intelligence, motivation and education
‡ inability to recognize phonemes has been shown to be the
best
predictor of reading disability
ƕ occipital lobe -identification of letters
ƕ inferior frontal lobe ± phonological processing
ƕ superior and middle gyri of the left temporal lobe ±
semantic processing
‡ developmental nonverbal learning disorder: right hemisphere
dysfunction. Characterized by poor fine motor control of the left
hand, deficits in visuoperceptual organization, problems with
mathematics, and incomplete or disturbed socialization.
‡ Music is represented predominantly in the right hemisphere,
but full complexity of musical ability involves both hemispheres
Emotion:
‡ derives from basic drives: feeding, sex, reproduction,
pleasure, pain, fear, and aggression
‡ drives centered in the limbic system
‡ distinct human emotions: affectation, pride, guilt, pity, envy,
and resentment ± largely learned, most likely represented in
the cortex
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‡ frontal cortex: regulation of drives
‡ left hemisphere: analytical mind, has limited emotional
repertoire. Damage: produces intellectual disorder & loss of
narrative aspect of dreams
‡ Right hemisphere: dominant for affect, socialization and body
image. Damage: produces affective disorders, loss of visual
aspect of dreams, and a failure to respond to humor, shadings
of metaphor, and connotations.
‡ Anosognosia: denial of illness and of the ability to move the
left hand in cases of right hemispheric injury.
‡ Temporal lobe: exhibits a high frequency of epileptic foci and
temporal lobe epilepsy (TLE)
ƕ proposed TLE personality ± hyposexuality emotional
intensity perseverative approach to interactions
(viscosity).
ƕ Left TLE - may generate references to personal
destiny and philosophical themes and may display a
humorless approach to life
ƕ Right TLE ± may display excessive emotionality,
ranging from elation to sadness
ƕ reverse TLE personality ± bilateral injury of the
temporal lobes. Lesion resembles the one described
in kluver-bucy syndrome
ƕ Kluver-Bucy syndrome: hypersexuality, placidity,
tendency to explore the environment with the mouth,
inability to recognize the emotional significance of a
visual stimuli and constantly shifting
attention(hypermetamorphosis)
‡ Prefontal cortices influence mood in a complementary way.
Activation of:
ƕ left prefrontal cortex ± lifts the mood. Lesion:
depression, uncontrollable crying
ƕ right prefrontal cortex ± causes depression. Lesion:
laughter, euphoria, and witzelsucht (a tendency to
joke and make puns)
‡ Papez 1973: delineated the limbic system.
‡ Papez circuit: hippocampus, fornix, mamillary bodies, anterior
nucleus of the thalamus, cingulate gyrus
‡ boundaries of limbic system was expanded to include:
amygdala, septum, basal forebrain, nucleus accumbens, and
orbitofrontal cortex.
‡ Amygdala: improtant gate through which internal and external
stimuli are integrated. Damage: ablate the ability to distinguish
fear and anger in other people's voices and facial expressions.
But preserved ability to recognize happiness, sadness, or
disgust
‡ Schizophrenia: affect, associations, ambivalence and autism.
Has reduction in brain weight of the gray matter and may have
reduced volume of the hippocampus, amygdala, and
parahippocampal gyrus. May have selective reduction in
frontal lobe activity.
Frontal lobe function
‡ region that determines how the brain acts on its knowledge,
constitute a category unto themselves.
Four subdivisions:
ƕ first 3: motor strip, supplemental motor area, and
broca's area
ƕ 4th, most anterior division ± prefrontal cortex
3 regions of the prefrontal cortex:
ƕ orbitofrontal
ƕ dorsolateral
ƕ medial
‡ frontal lobe injury impairs the executive functions: motivation,
attention, and sequencing of actions
‡ bilateral frontal lobe lesions: changes in personality ± how
people interact with the world
‡ Frontal lobe syndrome: slowed thinking, poor judgement,

decreased curiosity, social withdrawal, and irritability.
‡ Specific prefrontal lobe syndromes
Orbitofrontal region:
‡ causes disinhibition, irritability, lability, euphoria, and lack of
remorse.
‡ Insight and judgement are impaired; patients are distractable
‡ features are similar to: antisocial personality disorder,
intermittent explosive disorder, and episodic dyscontrol
syndrome
‡ may produce a state of ³pseudopsychopathy´
Dorsolateral region:
‡ executive headquarters of the brain
‡ lesions may lead to: deficiencies of planning, monitoring,
flexibility, and motivation.
‡ Patients may be unable to use foresight, and feedback to
maintain goal directedness, focus and sustained effort
‡ appears inattentive and undermotivated, cannot plan novel
cognitive activity, exhibits tendency to linger on a trivial thought
‡ may also produce mood disorders
Medial region:
‡ ablation of this region may produce profound apathy,
characterized by limited spontaneous movement, gesture, and
speech
‡ extreme: state of akinetic mutism, without any initiation of
activity at all
Development
‡ nervous system: CNS and PNS
‡ CNS: Brain and spinal cord
‡ PNS: all sensory, motor, and autonomic fibers and ganglia
outside the CNS
‡ development: both CNS and PNS arise form a common
precursor ± neural tube ĸ folding of neural plate ĸ ectoderm
‡ embryonic development:
ƕ neural tube itself ĺ CNS
ƕ ectoderm immediately superficial to the neural tube
ĺ neural crest ĺ PNS
Central Nervous System
‡ life cycle of a neuron: cell birth ĺ migration to the adult
positionĺ extension of an axon ĺ elaboration of dendrites ĺ
synaptogenesis ĺ onset of chemical neurotransmission
1.Individual neurons are born in proliferative zones located
along the inner surface of the neural tube
‡ peak of neuronal proliferation: middle of 2nd trimester.
250000
neurons born each minute.
2. First 6 mos of gestation: glial - guided (astrocytic glial fibers)
neuronal migration in the cerebral cortex
‡ heterotopia ± group of incorrectly placed neurons . Fails to
reach the cortex and reside in ectopic positions. Causes
epilepsy and highly associated with mental retardation
‡ many neurons lay an axon down as they migrate, while
others do not initiate axon outgrowth until they have reached
their cortical targets
‡ axons subsequently detach from the subplate neurons and
proceed superficially to synapse on the true cortical cells,
subplate neurons then degenerate
3.Synaptogenesis occurs at a furious rate from the 2nd
trimester through the first 10 years of life.
‡ Peak of synaptogenesis occurs within the first 2 postnatal
years: as many as 30 million synapses form each second
‡ ensheathment of axons by myelin begins prenatally; largely
complete in early childhood but does not reach its full extent
until the 30's
4.Onset of chemical neurotansmission
c
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Neurophysiology and Neurochemistry
‡ An important determinant of the quality of thought is the
efficiency of the information processing by individual neurons
‡ Single neurons communicate by:
ƕ interpreting their chemical environment
ƕ instantly changing chemical cues to electrical activity
for transport down axons
ƕ efficiently translating the electrical data into finely
modulated secreteable chemical emissions with
which to influence other neuronal or nonneuronal
cells
‡ Electrical impulses facilitate instantaneous responses
‡ Chemical mileu ± important to the maintenance of fidelity of
the brain's image of the world
‡ BASIC ELECTROPHYSIOLOGY
‡ Membranes and Charge
‡ Resting state: intracellular (-), extracellular (+)
‡ charge gradient is maintained across the hydrophobic plasma
membrane:
ƕ semipermeable, lipid bilayer with embedded
cholesterol molecules and numerous proteins (ion
pumps, ion channels, neurotransmitter receptors)
‡ Ion pumps and ion channels maintain gradient of cations:
ƕ potassium ions: 15 ± 20 times more concentrated
inside neurons
ƕ sodium ions: 8 ± 15 times less concentrated inside
neurons
‡ Principal ion pump: Na-K ATPase exchange pump
‡ Principal ion channels: Na, K, Ca, Cl
‡ hydrophobic neuronal membrane isolates positive and
negative ions
‡ charge can be released when channels
‡ open allowing the passage of ions through the membrane
‡ electrical potential follows the equations of Ohm's Law: E=IR
ƕ E: transmembrane potential
ƕ I: current
ƕ R: resistance
‡ Ion Channels
‡ Protein pores that allow the flow of ions unimpeded through
the membrane and cause changes in membrane potential
‡ selective for specific ions
‡ glycoproteins
‡ resting state: closed
‡ opens in response to:
ƕ binding of ligands into receptors: ligand ± gated ion
channels
ƕ changes in membrane potential: voltage ± gated ion
channels
‡ Ligand-gated ion channels
‡ 3 general types:
ƕ direct-coupled: neurotransmitter acts directly
ƕ G protein coupled: neurotransmitter ĺ receptor
protein ĺ activates G protein ĺ activates ion
channels
ƕ second-messenger-coupled: activated by a second
messenger product of some physically removed
receptor
‡ Ligands:
ƕ excitatory neurotransmitters ± opens cation
channels that depolarize the membrane and increase
likelihood of the generation of an action potential eicit
EPSP.
ƕ Inhibitory neurotransmitters ± open chloride
channels that hyperpolarize the membrane and

decrease the likelihood of an action potential. Elicits
IPSP.
ƒ CNS Ca channel blockers ± treatment of
bipolar disorder
ƒ Dantrolene ± skeletal muscle Ca channel
blocker, treatment of Neuroleptic malignant
sydnrome
‡ Action Potentials (AP):
‡ resting, intracellular: -70 to -80 mV
‡ action potential:
‡ brief (0.1 to 2 ms) wave of reversal of membrane potential
that moves along an axon
‡ ligand-gated ion channels open ĺ sodium enters the cell ĺ
inner surface of the membrane less negatively charged relative
to the outside ĺ opening of voltage-gated Na channels ĺ
inward flow of Na (+ charge inside) ĺ depolarization of
membrane and initiation of (AP)
‡ spike threshold ± the point at which the interior of the
membrane is sufficiently less negatively charged to cause the
opening of Na channels. Approx. -55mV
‡ ion channels:
ƕ initial: Na channels, makes the interior (+) charged
ƕ then, Ca2+ channels open, further contributes to the
spike of action potential. Also activates ion channels
that carry an outgoing flow of K+ ions
‡ afterhyperpolarization: result of activation of K+, inside of the
membrane is more negatively charged than baseline.
Contributes to the refractory period. Another action potential
cannot be generated during this period.
‡ Rate of local spread of an action potential determines the rate
of conduction of the impulse along the nerve.
‡ Myelin sheaths ± highly hydrophobic substance that
completely prevents passage of ions. Reduces the number of
times the AP must trigger neighboring voltage-gated ion
channels in order to conduct an impulse along that distance of
axon.
‡ Nodes of ranvier ± gaps of bare axonal membrane, separates
myelin sheaths.
‡ AP at nodes of ranvier ĺ AP jumps over myelin segment ĺ
next node of ranvier
‡ Transmission of the AP into chemical Neurontransmission:
‡ At synaptic terminus of the axon, AP triggers the release of
neurotransmitters into the synaptic cleft ĺ may act on other
neurons or muscles.
‡ Presynaptic nerve terminals contain voltage-gated Ca
channels ĺ locally raise intracellular Ca ĺ cascade of protein-
protein and protein- lipid interactions ĺ
neurotransmittercontaining
synaptic vesicles fuse with presynaptic membrane
ĺ release contents into synaptic cleft
‡ in muscles: AP ĺ opens voltage-gated Ca channels ĺ
triggers the movement of myosin on actin fibers (excitation ±
contraction coupling)
‡ SYNAPSES
‡ All or none phenomenon: once an action potential has been
triggered, it is propagated at full strength for the entire length of
the axon
‡ axon hillock ± originates AP, acted upon by excitatory and
inhibitory influences
‡ synapse ± site at which stimuli are given and received and
where the finest shadings of neuronal activity are negotiated
‡ components of the synapse:
ƕ axon terminal of the presynaptic neuron
ƕ synaptic cleft
ƕ dendrite of the postsynaptic neuron
‡ AP in presynaptic neuron ĺ AP moves down the axon ĺ
axon terminal or to other functionally similar regions of the
axons (axonal varicosities) ĺ AP causes the release of
c
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neurotransmitter (NT) molecules into the synaptic cleft ĺ NT
molecules diffuse across the synaptic cleft ĺ binds to their
specific receptors on the external membrane of the dendrite of
the post synaptic neuron
‡ types: depending on the location of the termination
ƕ axosomatic ± postsynaptic neuronal cell body
ƕ axoaxonic ± axon
ƕ axodentritic ± dendrite
‡ gap junctions ± electrical synapses that allow the direct
transfer of ions between 2 neurons as a form of intraneuronal
neurochemical communication
‡ cojoint synapses ± have both electrical and chemical
characteristics
‡ Only synapses of functional relevance survive into adulthood.
‡ Adult synaptic relationships are constantly remodeled through
increases and decreases in the size and strength of individual
synapses, also formation of new synapses and elimination of
unnecessary synapses.
‡ Mechanical adhesive properties: mediated by various
combinations of Ca-dependent cadherin family of adhesion
molecules
‡ Changes in structure: mediated by growth factors ± acts on
specific receptors to regulate protein-protein interactions and
to modify levels of gene expression
‡ N-methyl-D-aspartate (NMDA) glutamate receptors: essential
to certain forms of long term potentiation (LTP) in w/c
coordinated neuronal activity strengthens certain synapses.
‡ LTP ± proposed to be cellular correlate of long term memory
‡ Presynaptic Components
‡ contains the synthetic machinery responsible for the
synthesis of all NT except peptide NT, which are synthesizes in
the cell body
‡ NT synthesis stimulated by:
ƕ influx of Ca ions
ƕ variations in levels of the 2nd messenger cAMP
ƕ changes in levels of circulating hormones.
‡ Once synthesized, NT is packaged into synaptic vesicles
(may store a mixture of amine and peptide NT)
‡ Mitochondria: provide energy for synthesis, storage, release
and degradation of NT
‡ presynaptic membrane contains: ion channels ± trigger
vesicle release, NT receptors ± mediates feedback inhibition of
NT synthesis and release, NT transporters ± take NT up from
the synaptic cleft for recycling or degradation.
‡ NT storage vesicles in the presynaptic terminal fuse with the
presynaptic membrane and release their component into the
synaptic cleft: Exocytosis
ƕ Synapsins and Rab3: control the localization of
vesicles
ƕ synaptotagmin and synaptobrevin: components of
the vesicle membrane
ƕ neurexins and syntaxins: components of the plasma
membrane, mediate the fusion of the inner surface of
the presynaptic membrane
ƕ synaptophysins: aids in the creation of a pore in the
presynaptic membrane
‡ Once a monoamine NT such as norE, dopamine, or serotonin
has been released into the synaptic cleft, it acts until it diffuses
away, or moved by reuptake mechanisms
‡ specific presynaptic transmembrane transporter molecules
return free monoamine NT to the nerve terminal where they
are:
ƕ repackaged into vesicles for release in response to
subsequent AP
ƕ degraded into monoamine oxidases (MAOs)
‡ transporters ± sites of major mechanism of actions of both
therapeutic and illicit drugs
ƕ Tricyclic antidepressants ± inhibits norE and
serotonin reuptake mechanisms

ƕ Selective serotonin reuptake inhibitors (SSRIs) ±
detects the inhibition of monoamine reuptake
through transporters
ƕ Cocaine ± blocks all 3 monoamine transporters
‡ degradation of recycled biogenic amine NT is principally
mediated by MAOs attached to the outer mitochondrial
membrane.
‡ MAOA ± metabolizes norE and serotonin
‡ MAOB ± metabolizes dopamine
‡ Synapse
‡ synaptic compartment: the space between the pre and
postsynaptic membranes. Contains a mixture of NT with the
greatest influence on thought and behavior
‡ NT are available to act on specific receptors and to initiate or
inhibit the generation of AP on postsynaptic cell
ƕ amino acids: glutamate, GABA, glycine, aspartate,
homocysteate
ƕ biogenic amines: norE, serotonin, dopamine, epi,
acetylcholine, histamine
ƕ neuropeptides: vasopressin, oxytocin, enkephalins,
endorphins, substance P, neurontensin, etc..
ƕ nucleotides: adenosine, cAMP
ƕ gases: NO, CO, NH3, prostaglandin
‡ synaptic cleft of cholinergic synapses harbours
acetylcholinesterase, which inactivates aCh by cleaving it into
acetate and choline
‡ concentrations of NT are in the synaptic left regulated by
ƕ feedback inhibition of transmitter release
ƕ reuptake into the presynaptic terminal by transporter
molecules
‡ Postsynaptic Components
‡ Receptors ± sites of action of many of the psychotherapeutic
and psychoactive drugs
‡ function: alter the electrical transmembrane potential - either
to increase or to decrease the likelihood of triggering an AP
‡ once the threshold of the action potential is reached at the
axon hillock, the all-or-none action potential is initiated by the
opening of voltage-gated Na channels ± there virtually no
chance for modification of the impulse
‡ response to a constant NT:
ƕ supersensitivity ± greater than usual
ƕ subsenisitivity ± less than usual
‡ sensitivity of a receptor may be due to:
ƕ number of receptors present
ƕ affinity of the receptor for the NT
ƕ efficiency with which the binding of the NT to the
receptor is translated into an intraneuronal msg.
‡ 2 types of NT receptors:
ƕ seven-transmembrane-domain receptors: requires G
proteins to open channels.
ƕ ligand-gated ion channels: the channels is an
integral part of the complex that binds the ligand
‡ intracytoplasmic loop
ƕ 1st-smallest
ƕ 2nd- fairly large
ƕ 3rd- largest
‡ tyrosine kinase receptors ± does not cause changes in
membrane potential. Has extracellular ligand-binding
component, single transmembrane domain, and intracellular
tyrosine kinase ± which phosphorylates both itself and other
cytoplasmic proteins ĺ triggers a cascade of intracellular
phosphorylations ĺ changes in gene expression.
‡ Tyrosine kinase receptors bind growth factors and mediate
the plasticity of synaptic associations
ƕ Nerve growth factor (NGF)
ƕ Brain-derived neurotropic factor (BDNF)
‡ Postsynaptic cells are also regulated by circulating hormones
(thyroid hormone, steroids) ± hormones diffuse through the
c
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membrane ĺ bind to cytoplasmic receptors ĺ translocated 1. 
 
 -the best known and most understood
into the nucleus ĺ regulate gene expression neurotransmitters because they were the first to be discovered
 -constitute the neurotransmitter substance in only a small
5
   percentage of neurons
-family of guanisine triphosphate (GTP)-binding proteins with - synthesized in a discrete nucleus of neurons from which
similar structures axons project widely throughout the brain and spinal cord
-interact with members of the very large family of seven - exert a disproportionate influence on the activity of the brain,
transmembrane-domain receptors of w/c the adrenergic and they are of central importance to the pharmacological
receptor is a prototype therapy of thought, mood, and anxiety disorders
-consist of 3 smaller proteins, alpha, beta and gamma
subunits *Dopamine, norepinephrine, and epinephrine are products of
-when an intact G protein binds to a receptor, the receptor the catecholamine synthetic pathway
assumes a state w/ a high affinity for the neurotransmitter
molecule, triggering the replacement of GDP with GTP on the *Serotonin, acetylcholine, and histamine are derived from
alpha subunit, thereby destabilizing the associations among distinct precursors
the neurotransmitter, the receptor and the G protein
-GTP associated alpha subunit is the active fragment involved 2. #


- late to be discovered
in activating or inhibiting a particular effector molecule - present in upward of 70 percent of neurons
-alpha subunit has the ability to convert GTP to GDP - two major amino acid neurotransmitters are GABA and
-activity of GTP-associated alpha subunit is stopped when glutamate
GTP is converted to GDP GABA- inhibitory amino acid
a -stimulation of adenyl cyclase activity Glutamate-excitatory amino acid
b) -inhibition of adenyl cyclase activity
c)
  -stimulation of phosphoinositol 2nd 3.  
 -As many as 300 peptide neurotransmitters may
messenger be in the human brain
system - short protein consisting of fewer than 100 amino acids
 -made in the neuronal cell body by the transcription and
+%"$)%++%5%(+ translation of a genetic message
1,





#)

5) -stored in synaptic vesicles and are released from the axon
*cAMP-produced from ATP by the enzyme adenyl cyclase terminals
-binds to CREBP -activity is terminated by the action of enzymes, peptidases,
a) Gs protein-stinulates activity of adenyl cyclase which cleave the peptides between specific amino acid
b) G1 Protein-inhibits the activity of adenyl cyclase residues

2. 
 3 
 $#50stimulates formation of NO and "5%#)%+
may trigger excitotoxic cellular damage $
 
*Primary and alternative pathways for the formation of
3. 



) 
  catecholamines:
-receptor-activated enzyme phospholipase C converts (1) tyrosine hydroxylase
membrane lipid (phosphatidylinjositol 4,5-biphosphate) into IP3 (2) aromatic amino acid decarboxylase
and DAG (3) dopamine-I2-hydroxylase
a) 3- cause the release of calcium from intraneuronal stores (4) phenylethanolamine-N-methyltransferase
b) $#5-activate a specific protein kinase (5) nonspecific N-methyltransferase in lung and folate-
4. %



 dependent
6. 5  N-methyltransferase in brain
7. 8#90+!#!-receptor for cytokines (6) catechol-forming enzyme


  9   **actions of dopamine are terminated by Ñ 
 
- catalyze the transfer of the terminal phosphate group of ATP 1. can be taken back up into the presynaptic neuron and
onto protein molecules recycled as a neurotransmitter( reuptake mechanism)
Tyrosine kinases-activated by growth factors binding to specific - Reuptake occurs by the passage of the dopamine molecule
transmembrane receptors from the synaptic space, through the presynaptic dopamine
*lithium therapy has been shown to reduce the activity of transporter, into the intracellular space, where it is packaged
protein kinase in concert with its salutary effects on bipolar into vesicles
disorder
 2. dopamine can be metabolized
% ("!(#+)!!%(+ - Ñ
 


 







 


 



Criteria




 
 

 

 

 !

1. The Molecule is synthesized in the neuron a) )#"is localized on the outer mitochondrial membrane,
2. The molecule is present in the presynaptic neuron and is principally in the presynaptic terminal, where it acts on
released on depolarization in physiologically significant dopamine that has been taken up into the presynaptic terminal
amounts. but not yet
3. When administered exogenously as a drug, the exogenous repackaged into vesicles
molecule mimics the effects of the endogenous b) ")!is a soluble enzyme localized in the cytoplasm of the
neurotransmitter. postsynaptic cell and of glial cells and, possibly also,
4. A mechanism in the neurons or the synaptic cleft acts to extracellularly
remove or deactivate the neurotransmitter
×
 


3. )2
!  *$
$4

-stimulate the formulation of cAMP by

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activating the stimulatory G protein, Gs * major concentration of noradrenergic (and adrenergic) cell
*D2, D3, and D4 
  bodies that project upward in the brain is in the



$Ñ
 -inhibits the formation of cAMP by activating the
    
inhibitory G protein, Gi, and some data indicate that the D3 and -axons of these neurons project through the 
.   
D4 receptors act similarly 
   
 
 1 
  
-prominent in the striatum (caudate nucleus and putamen) 
  
$3
 -concentrated in the nucleus accumbens *catecholamines are synthesized from   , and the rate
$o
 -concentrated in the frontal cortex limiting enzyme is   
 1 
**$Ñ
 -associated with a greatly reduced risk of -In neurons that release norepinephrine, the enzyme
development of parkinsonian side effects and tardive
  :;0
 1 
 
   
dyskinesia    
-not only do they treat the positive symptoms of schizophrenia, -neurons that release dopamine lack this enzyme
effectively treated by pure D2 receptor antagonists (psychosis, - In neurons that release epinephrine, the enzyme
hallucinations, agitation), they also improve the negative phenylethanolamine-N-methyltransferase (PNMT) converts
symptoms of schizophrenia (blunted affect, ambivalence, norepinephrine into epinephrine
catatonia) *Neurons that release either dopamine or norepinephrine do
*Amphetamines cause the release of dopamine, and cocaine not have PNMT
blocks the uptake of dopamine 


 that are most associated with
- increase the amount of dopamine present in the synapse norepinephrine:
*Cocaine and methamphetamine (Desoxyn) are among the · classic antidepressant drugs
most addicting substances · tricyclic drugs
*dopaminergic systems may be particularly involved in the · MAO inhibitors (MAOIs)
brain's so-called  -
    0 6   , and · venlafaxine (Effexor), mirtazapine (Remeron), bupropion, and
this involvement may explain the high addiction potential of nefazodone (Serzone)
cocaine *



  .1     
 .7
,
* dopamine transporter can be blocked by    block the reuptake of norepinephrine (and serotonin) into the
r   presynaptic neuron, and the MAOIs block the catabolism of
- transporter is the portal of entry of the neurotoxin norepinephrine (and serotonin)
methylphenyltetrahydropyridine (MPTP), which may cause 
parkinsonism by killing the nigral dopaminergic neurons     

   
 -’"



  


 
was based on
$  

    the observation that the tricyclic drugs and the MAOIs are
Dopamine may be involved in: effective in alleviating the symptoms of depression
a)mood disorders 
b) depression and high in mania
+    
c) schizophrenia 2   .   


 
*upper pons and the midbrain specifically, the median and
3)   $  
!
 dorsal raphe nuclei and, to a lesser extent, the caudal locus
1.   



- projects from its cell bodies in the ceruleus, the area postrema, and the interpeduncular area
substantia nigra to the corpus striatum -these neurons project to the basal ganglia, the limbic system,
-when the D2 receptors at the end of this tract are blocked by and the cerebral cortex
classic antipsychotic drugs, Parkinsonian side effects emerge
- In Parkinson's disease the nigrostriatal tract degenerates, 
× 
resulting in the motor symptoms of the disease -



 
   )#", respectively, block the
- may somehow be involved with the control of mood uptake and the metabolism of serotonin and norepinephrine,
thus increasing the concentration of both neurotransmitters in
2.    
 

- projects from its cell the synaptic cleft
bodies in the ventral tegmental area (VTA), which lies adjacent - 1   is one of the selective serotonin reuptake
to the substantia nigra, to most areas of the cerebral cortex, inhibitors (SSRIs) that are used in the treatment of depression
and to the limbic system -Other drugs in that class include paroxetine (Paxil), sertraline
- tract may be involved in mediating the antipsychotic effects (Zoloft), fluvoxamine (Luvox), and citalopram (Celexa), all of
of antipsychotic drugs which are usually associated with minimal adverse effects,
especially in comparison with the tricyclic drugs and the MAOIs
3.
 

- cell bodies of the are in the 
arcuate nucleus and the periventricular area of the 
 

  
hypothalamus, project to the infundibulum and the anterior *principal association of serotonin is with
  , as
pituitary suggested in the   
      . 

- dopamine acts as a release-inhibiting factor in the tract by
 

inhibiting the release of prolactin from the anterior pituitary -this hypothesis is simply that
   is associated with
-patients who take dopamine receptor antagonists often have          and that   is associated with  
roughly threefold elevated prolactin levels because the 

blockade of dopamine receptors in the tract eliminates the     
inhibitory effect of dopamine <       postulates that low levels of
 serotonin permit abnormal levels of norepinephrine to cause
    
%  -catecholamines depression or mania
- norepinephrine system and the epinephrine system are also
referred to as the noradrenergic system and the adrenergic %!$%% ("!(#+)!!%(+
system, respectively. %
 "
- analgesic and psychological effects
-receptors are referred to simply as adrenergic receptors 

c
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 +
 - primary neurotransmitter in most primary classic antipsychotic drugs (e.g., haloperidol)
afferent sensory neurons and in the striatonigral pathway * Drugs that increase cholinergic activity by blocking
-most prominently associated with mediation of the perception breakdown
of pain. by acetylcholinesterase (e.g., donepezil [Aricept]) have been
-Abnormalities affecting substance P have been hypothesized shown to be effective in the    .
  . 
for Huntington's disease, dementia of the Alzheimer's type, and #7  = 
mood disorders 
 #

  

   

    - involved in the pathophysiology of *most common association with acetylcholine is
  .
schizophrenia, mostly because of its coexistence with  #7  = 
  
 
dopamine in some axon terminals 
-preliminary reports suggest that neurotensin-related peptides
5##- found almost exclusively in the CNS, and it does not
or drugs have beneficial effects for some psychotic symptoms cross the blood-brain barrier
 - highest concentrations in the midbrain and diencephalon, with

  
 6  - involved in the pathophysiology of lower amounts in the cerebral hemispheres, the pons, and the
schizophrenia. CCK has also been implicated in the medulla
pathophysiologies of eating disorders and movement disorders -synthesized from glutamate by the rate-limiting enzyme
-causes anxiety and triggers panic attacks in people with panic glutamic acid decarboxylase (GAD), which requires pyridoxine
disorder (vitamin B6) as a cofactor
 -primary neurotransmitter in intrinsic neurons that function as
 +   - also known as growth hormone-inhibiting local mediators for the inhibitory feedback loops
factor -commonly coexists with biogenic amine neurotransmitters,
-implicated in Huntington's disease and dementia of the glycine, and peptide neurotransmitters, including somatostatin,
Alzheimer's type NPY, CCK, substance P, and vasoactive intestinal peptide
(VIP)
. '    
 "1
 - involved in the regulation of * thought to suppress seizure activity, anxiety, and mania,
mood and most recently, social behaviour are both synthesized considerable effort has been devoted to synthesizing drugs
in the hypothalamus and are released in that potentiate GABA activity
the posterior pituitary ** focused on its potential role in the pathophysiology of
  1 
    
 *- stimulate the appetite, and development
 

of neuropeptide Y receptor antagonists is an active area of 
interest for obesity researchers 5 - synthesized from glucose and glutamine in
 presynaptic neuron terminals and is stored in synaptic vesicles
#)"#$% ("!(#+)!!%(+ - primary neurotransmitter in cerebellar granule cells, the
5
 - synthesized primarily from serine by the actions of striatum,
serine trans-hydroxymethylase and I2-glycerate the cells of the hippocampal molecular layer and entorhinal
dehydrogenase, both of which are rate limiting cortex, the pyramidal cells of the cortex, and the
 thalamocortical and
& - Neurons that release histamine as their corticostriatal projections
neurotransmitter are located in the hypothalamus and project -release is stimulated by 
 
to the cerebral cortex, the limbic system, and the thalamus ** major pathophysiological conditions currently associated
- H1-receptor stimulation increases the production of IP3 and with
DAG the glutamate systems are 1
  1


7  
-H2 stimulation increases the production of cAMP **Excitotoxicity relates to the hypothesis that excessive
-H3 receptor may regulate vascular tone stimulation
*blockade of H1 receptors is the mechanism of action for of glutamate receptors leads to prolonged and excessive
allergy medications and is partly the mechanism for commonly intraneuronal concentrations of calcium and NO
observed side effects (e.g., sedation, weight gain, and
hypotension) of some psychotropic drugs .      
  j%"!$%+

#

   - purine adenosine inhibits the release of other
CNS Cholinergic Tracts neurotransmitters and ATP
-group of cholinergic neurons in the nucleus basalis of Meynert Ñ% ("!("&#!"(+
projects to the cerebral cortex and the limbic system - growth factors that allow neurons to regenerate their
-additional cholinergic neurons in the reticular system project to axon
the cerebral cortex, the limbic system, the hypothalamus, and - bind to the tyrosine kinase receptors
the thalamus - release happen during unstimulated resting
*Some patients with dementia of the Alzheimer's type or Down conditions
syndrome appear to have specific degeneration of the neurons - NGF (Nerve Growth Factor): is the most widely-
in the nucleus basalis of Meynert known
 - CNTF (Ciliary Neurotrophic Factor)
  
(
  - GDNF (Glial Cell-line Neurotrophic Factor)
a) Muscarinic- antagonized by atropine and by the - IGF (Insulin Growth Factor)
anticholinergic drugs 35#+%+
b) Nicotinic- ligand-gated ion channels that have - Nitric Oxide: acts as both intraneuronal second
the receptor site directly on the ion channel itself messenger and neurotransmitter; excessive exposure
* most common use of anticholinergic drugs in psychiatry is in to glutamate shall cause NO to be metabolized to
   .     caused by the use of

c
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 toxic free radicals which may injure or kill cells
through excitotoxicity
 
o%"+#"$+
 of axonal projections to inappropriate targets.
- metabolites of arachidonic acid, prostaglandins,
prostacyclins, thromboxane, and leukotrienes
4%$"##"$+
- cannabinoids: active ingredients in marijuana
- anandamides: generally exhibit pharmacological
— During later part of the development, the connections of
particular neurons are focused by the


— role of any brain region or group of neurons in the
production of specific behaviors or in the pathophysiology
of a given neuropsychiatric disorder
- must be considered within the context of the 
 
 


    

 
effects that are less potent (lowering intraocular 
 
pressure, decreasing activity level, and relieving pain)
>+5)#(%%!"(+
- receptor site binds pentazocine (Talwin) and
haloperidol
 
 
 
 -process involving the release ability to study specific genetic linkages among individuals
of a neurotransmitter by one neuron and the binding of the
neurotransmitter molecule to a receptor on another neuron.
affected by most drugs used in psychiatry
— Older antipsychotics, (not the serotonindopamine
antagonists)
-believed to exert their effects mainly by blocking
dopamine type 2 (D2) receptors
— antidepressants
-increase the amount of serotonin or norepinephrine, or
both, in the synaptic cleft
— benzodiazepine anxiolytics
- exert their effects on the GABAA receptors that are
linked to chloride ion channels
 endocrine dysfunction
 


 — The interactions b/w the neuroendocrine and central
- modulates the response of a neuron to a neurotransmitter
- modulatory effect may be present for a longer time
- substance may have an effect on a neuron over a long period
of time, and that effect may be more involved with fine tuning
than
with activating or directly inhibiting the generation of an action
potential
 variables in psychiatric conditions
 

 —
- released into the bloodstream rather than into the
extraneuronal space in the brain
-once in the bloodstream, the neurohormone can then diffuse
into the extraneuronal space and have its effects on neurons
% ("5%%!+
— alterations in gene expression
- occur both during development and in adulthood and
may be the bases for: (1) abnormal and normal
development, and (2) for abnormal and normal adaptation
to stress 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 ĺ patterns of activation: mediated
by the connections among specific brain structures
— every function of the human brain is a consequence of the
activity of specific neural circuits
- circuits form as a result of several 

 suicidal ideation
— POPULATION GENETICS
- provided some of the first objective data that mental
illnesses were biological illnessesĺhelping to
destigmatize these human conditions
- application of molecular neurobiological tools: led to the
and groups of individuals
- application lead to the identification of a specific gene or
genes as causative agents for specific mental disorders
+*&"% ("%$"("j"5*
- 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
— 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
nervous sys.:
- psychiatric symptoms that accompany
some hormonal disorders (e.g.,
depression in Cushing's syndrome)
- in the identification of disorders wherein
neuroendocrine regulation is utilized as
potential markers for state or trait
Pathological alterations in hypothalamic-pituitary-adrenal
function have been associated with mood disorders,
posttraumatic stress disorder, 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,

 
— In early development, some axons initially produce an ,+*&"% (")) "j"5*
      
 - nervous system and the immune system represent two

 

 
 


than are present in networks within the body ĺ each contains a massive diversity
the adult brain. of cell types and uses a large pharmacopoeia of chemical
signals

c
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 This model offers no guidance on when and which
— classical conditioning paradigms ĺ associated with psychosocial factors are important ± MD left with the
suppression or enhancement of the immune response impression that they must know everything about the px ± will
— stressful life events ĺ Ĺ susceptibility to infectious
focus instead on physical pathology and the use of biological,
diseases
— academic/examination stress in medical students physical interventions
A showed Ļ 
   

,  

 
, 
 
 
 ,
and 
 
 #$'#!#5%+ $+#$'#!#5%+
— 

 results from a combination of: Applicable to chronic Not applicable to acute
- direct effects of an injurious event on conditions conditions
various cell types, and Provides a conceptual Not a template for practicing
- effects of inflammatory mediators on framework for disparate med or txting individual pxs
neurons and supporting cells information
— 
  

 Reminds the MD that there Can¶t be a substitute for a
-in some cases of schizophrenia can be more impt. Issues relationship that reflects
— 

  beyond purely biological warmth, genuine concern and
-may contribute to the pathophysiology of depression mutual trust

,"j"5#j(&*!&)+
&("""j"5* + / influences on a person¶s mental and physical
health    - sick role, role that society ascribes
— circadian biological rhythms
A are set by both internal and external forces,
generally called è
 (time givers, time )
 .  
 
clues, synchronizers) - Guides
— zeitgebers - One is not intrinsically superior over the other
A principally emanating from pontine reticular - May be used from all four for a single px visit
formation and suprachiasmatic nuclei of the - Difficulties most likely to arise w/ the MD who is rigidly fixed.
hypothalamus
— Phase advance or Phase delay PATERNALISTIC MODEL
— Depression is the most commonly associated symptom in - MD knows best
biological rhythm disruption - Px is expected to comply without question

INFORMATIVE MODEL
"j +"
- All available data is freely given but the choice is left wholly
Understanding the neurobiological bases for psychiatric up to the px
disorders requires an appreciation of the major principles
governing the functional organization and connections in the INTERPRETIVE MODEL
human brain, - MD who come to know their px better amd make
recommendations that take into account the unique
characteristics of the individual patient
$"!"(0#!%!?(%j#!"+&
Px are most tolerant of the therapeutic limitations of medicine DELIBERATIVE MODEL
when there is mutual respect between both parties. - MD act as a friend or counsellor

(  TRANSFERANCE AND COUNTERTRANSFERANCE

- harmonious responsiveness that promotes the dev¶t of a - Originating in psychoanalytical theory
constructive therapeutic relationship
Transference
- implies understanding and trust
- Unconsciously attributing to their MD aspects of important
past relationship
 
 


1) Biological system ± the anatomical, structural and molecular COUNTERTRANSFERENCE
substrates of disease and its effects on px¶s biological - Is when MD unconsciously ascribes motives or attributes to
functioning px that comes from MD¶s past relationships
2) Psychological system ± the effects of psychodynamic
factors, motivation and personality on the experience of and
reaction to illness
3) Social system ± cultural, environmental, and familial PSYCHIARTIRC VERSUS MEDICAL SURGICAL
influences on the expression and experience of illness INTERVIEWS
3 FXNS of medical interview:
*The model does not treat medical illness as a direct result of a 1) assess the nature of the problem
person¶s psychological or sociocultural make up ± instead 2) develop and maintain therapeutic relationship
3) communicate information and implement a txt
promotes a more comprehensive understanding of dse and txt.
— These fxns are exactly the same as those psychiatric and
surgical interviews
 
  
 



c
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— Also universal are predominant coping mechanisms, both
adaptive and maladaptive ± must anticpated by the MD for
tx to be effective
2 major technical goals of psychiatric interviews:

1) Recognition of the psychological determinants of behaviour
2) Symptom Classification

STRATEGIES IN DEV¶T OF RAPPORT
1. putting pxs and interviewers at ease
2. finding px¶s pain and expressing compassion

3. evaluating px¶s insight and becoming an ally
4. showing expertise
5. establishing authority as physicians and therapists

6. balancing the roles of emphatic listener, expert and authority
BEGINNING THE INTERVIEW
— Provides a powerful first impression; can affect the way

the remainder of the interview proceedings.
— Meant to point out to a Px something that the MD thinks
the Px is not paying attention to, is missing, or is in some
way denying
>,.

— MD attempts to get details from Px about what they have
already said
,   
— Used when a MD states something about the Px¶s
behavior or thinking that the Px may not be aware of
U,+
— MD can take a moment and briefly summarize what a Px
has said thus far
l,%1 
— MD explains treatment plans to Px in easily
understandable language and allow Px to respond and
ask questions
B,! 
— Allow MD to convey the idea that enough information has
been obtained on one subject, that MD¶s
THE INTERVIEW PROPER ,+ .0(  


 - topics or subjects — Limited, discreet self-disclosure by MDs may be useful in


 0 what occurs non verbally between doctor and certain situations, and MDs should feel at ease and
patient communicate a sense of self-comfort
- what is happening in the interview beneath the Ñ,
 (  .

 
surface — allows Px to feel comfortable telling the MD anything, even
- involves feelings and reactions that are about such things as noncompliance with Tx
unacknowledged or unconscious ĺ body language, 3,( 

trivial remarks, and apparently casual aides — Truthful reassurance of a Px can lead to increased trust
and compliance and can be experienced as an empathic
+%!%&@ %+

   -!
 A  response of a concerned MD
1. Establish rapport as early in the interview as possible. o,#


2. Determine the patient¶s chief complaint.
3. Use the chief complaint to develop a provisional differential
diagnosis.
4. Rule the various diagnostic possibilities out or in by using
focused and detailed questions.
5. Follow up on vague or obscure replies with enough
— To be effective and to be perceived as empathic rather
than inappropriate or intrusive, the advice should be given
only after Px are allowed to talk freely about their
problems so that MDs can have adequate information
based from which to make suggestions
4,%
     -
persistence to accurately determine the answer to the — MDs want Pxs to leave an interview feeling understood
question. and respected and believing that all the pertinent and
6. Let the patient talk freely enough to observe how tightly the important info has been conveyed to an informed,
thoughts are connected. empathic listener
7. Use a mixture of open-ended and close-ended questions.
8. Don¶t be afraid to ask about topics that you or the patient ")j#%
may find difficult or embarrassing. — Also known as adherence
9. Ask about suicidal thoughts. — Degree to which a Px carries out the clinical
10. Give the patient a chance to ask questions at the end of recommendations of a treating MD
the interview. — Compliance increases when:
11. Conclude the initial interview by conveying a sense of MD has characteristics as
confidence and, if possible, of hope. enthusiasm and nonpunitive
attitude
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Px have older doctors with more
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experience
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Increased amount of time spent
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talking to the Px
Short waiting room time
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A 
 Increased frequency of visits
Ñ,( .

 — Other strategies to improve compliance include asking the
— MD repeats to the Px, in a supportive manner, something Px:
that the Px has said To describe what they believe is
3,

 wrong with them and what should
— MD helps Px continue in the interview by providing both be done
verbal and nonverbal cues that encourage Px to keep What they understand to be the
talking reaons for the MD¶s
o,+
 recommendations
— May be constructive and in certain situations, may allow What they see as the risks and
Px to contemplate, cry, or just sit in an accepting, benefits of following prescribed Tx
supportive environment in which the MD makes it clear — Common errors of Pxs:
that not every moment must be filled with talk - not taking medications for as long as
4,
.

 they should

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- not taking the proper amount of their — Once a Px enters into a contract to receive care from a
medication each day particular MD, that MD is responsible for having a
A it would be helpful to print the instructions on a mechanism in place for providing emergency service
piece of paper and ask the Px to read them back outside scheduled appointment times
A ask the Px specifically and in what amounts the
medication is to be taken   -0 
— Pxs must be assured that regardless of what occurs in the
— Some Px deliberately change the Tx regimen course of a particular MD-Px relationship, their care will be
- not showing up for appointments ongoing
- taking medications in a manner different
from the recommended    
+
   -+ 
A MD must negotiate a compromise with the Px — Problem Px: difficult to work with; engage in power
A They must specify together what they can expect struggles, are demanding or uncooperative
from each other & 
 
— Have a dramatic, emotional, and impressionalistic style
— Some factors in Px compliance issues: $ 
 
— MD-Px relationship or MD-Px match — Need an inordinate amount of attention and yet never
A One of the most important factors seem reassured
A Compliance decreases when MD and Px have $ 
  
different priorities and beliefs, different styles of — Have a difficult time delaying gratification and demand that
communication, and different medical their discomfort be eliminated immediately
expectations 

 
A Compliance increases when MD explains to the — act as though they are superior to everyone around them
Px the value of a particular Tx outcome, and including the doctor
emphasizes that following the recommendation  
 
will produce this outcome; also when Px know — do not appear to need/want to make contact w/ other
the names and effects of each drug they are people
taking — intimate contact with doctor is viewed with distaste
— Px¶s subjective feelings of distress or illness as opposed to — some receive the pyschiatric diagnosis of schizoid
MD¶s often objective medical estimates of the disease and personality
required therapy — withdrawn, absorbed in a world of fantasy and unable to
A Px who believe they are ill tend toward talk about their feelings
compliance — doctors should treat these px¶s with much respect for their
A Asymptomatic Px are at greater risk for privacy as possible and should not expect them to
noncompliance respond to the doctor¶s concern in kind
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    — orderly, punctual and so concerned with detail that they
  
 
 
  often don¶t see the larger picture
 & 0( 2
   
+%++ %++*&#!(* — appear to communicate only through a long litany of
 complaints and disappointments
  )   
MD must openly discuss payment of fees — have antisocial personality traits
 . $..   

6 

 .
 — difference in race, nationality, religion and other significant
— Psychiatrists should discuss the extent and limitations of cultural differnces bet the px & doctor can impair
confidentiality with Pxs so that Pxs are clear about what communication, interfere in establishing rapport, & harbor
can and cannot remain confidential misunderstanding
— The Px must give permission for the use of medical
records: +    
 
who has access to the Px¶s medical a) required for the practice of medicine: (1) vast amt of
records knowledge & skills, (2) capacity to balance compassionate
information required by insurance concern with dispassionate objectivity, (3) wish to relieve pain
companies w/ ability to make painful decisions, (4) desire to cure & control
degree to which the Px¶s case will w/ an acceptance of one¶s human limitations
be used for teaching purposes b) learning to balance this interrelated aspects of physician role
is essential to allow the doctor to cope productively w/n daily
+   work that involves illness, pain, sadness, suffering, & death
— It is both commonplace and necessary for doctors in c) lack of balance results to a physician feeling overwhelmed &
training to receive supervision from experienced MDs depressed
d) a sense of futility & failure can begin to permeate a
)
#   
j  .+   physician¶s attitude, setting the stage for frustration & anger w/
— The Px needs to be informed about the MD¶s policies for one¶s profession, pxs, & self
missed appointments and length of sessions e) many people drawn to medicine are: perfectionistic,
— The Px must know in advance to make an informed demanding of themselves, attentive to details ± qualities are
decision about whether to accept the MD¶s policy or adaptive, probably necessary but need to be balance w/ self-
choose another MD knowledge, humility, humor, & kindness

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 C@  . 
 
Imperturability Ability to maintain extreme calm
& steadiness
Presence of Mind Self-control in an emergency or
embarrassing situation so that
one can say or do the right thing
Clear Judgment Ability to make an informed
opinion that is intelligible& free
of ambiguity
Ability to Endure Capacity to remain firm & deal
Frustration w/ insecurity & dissatisfaction
Infinite Patience Unlimited ability to bear pain or
trial calmly
Charity towards others To be generous & helpful,
especially toward the needy &
suffering
The search for absolute To investigate facts & pursue
truth reality
Composure Calmness of mind, bearing &
appearance
Bravery Capacity to face or endure
event w/ courage
Tenacity To be persistent in attaining
goal or adhering to something
valued
Idealism Forming standards & ideals &
living under their influence
Equanimity Ability to handle stressful
situations w/ an undisturbed,
even temper

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