Sensory system Human Physiology

1. GETTING INTRODUCED TO THE NERVOUS SYSTEM
• History of Neurobiology
• Charaka , an ancient Indian physician specified SHIRA ( HEAD
) as the part in which life stays , and to which all senses
belong .
• Other scientists like Aristotle ( 4th century BC ) and Galen (
2nd century AD ) also talked about nerve conduits etc .
• There was a long gap of almost 1000 years during which
nothing notable happened .
• A significant landmark in neurobiology was the European
book by Rene Descartes ( 1596-1650 ) –he talked about a
vital fluid which caused muscle contraction .

2. HISTORY OF NEUROBIOLOGY ( CONTD . )
• Luigi Galvani ( 1737-1798 ) demonstrated ANIMAL
ELECTRICITY )
• Du Bois Reymond ( 1818-1896 ) showed that messages are
conveyed by nerves through electrical impulses .
• Camillo Golgi ( 1873 ) dicovered a simplified neuronal
network by silver staining of the brain .
• Santiago Ramon Cajal further modified staining techniques
• In 1906, Golgi and Cajal shared the Nobel Prize for neuronal
structure although they had different concepts .
• Application of electron microscopy to neuronal tissue in the
1950s revealed the existence of the synaptic cleft .

3. Parallel Processing
• The information which results in a reflex may also be
conveyed to higher levels of the CNS and the same message
is generally handled by more than one pathway – this is
defined as PARALLEL PROCESSING .

4. THE NEURON
• Neuron is the basic stuctural and signal processing unit of
the nervous system .
• It has a cell body , the extensions which specialize in
receiving messages which are called DENDRITES and
extensions which transmit messages from the neuron
known as AXONS .
•

5. SYNAPSE
• Neurons transmit and process information across junctions
called synapses
• Usually a one way conduction
• Synaptic transmission may be either chemical or electrical .

6. ORGANIZATION OF THE NERVOUS SYSTEM
• The nervous system has an axial organization .
• The CNS or the central nervous system run along the midline
, receives information through the sensory nerves and sends
messages through the motor nerves .
• The sensory and the motor nerves constitute the peripheral
nervous system ( PNS ) .
• The simpler form of processing of information results in
reflex actions ; elaborate processing at cortical level results
in conscious behaviour .
• The basic stuctural and signal processing unit of the nervous
system is the neuron .

7. Types of Synapses
1. Axodendritic
2. Axoaxonal
3. Axosomatic

8. Presynaptic and Postsynaptic Structure and Function
1. Each presynaptic terminal of a chemical synapse is
separated from the postsynaptic structure by a synaptic
cleft i.e 20-40nm wide .
2. Across the synaptic cleft are many neurotransmitter
receptors in the postsynaptic membrane and usually a
postsynaptic thickening called postsynaptic density .
3. The postsynaptic density is an ordered complex of specific
receptors , binding proteins and enzymes induced by
postsynaptic effects .

9. Electrical Events In Postsynaptic Neurons
• Penetration of an alpha – motor neuron is a good example of
the tecniques used to study postsynaptic electrical activity .
• When an impulse reaches the presynaptic terminal , an
interval of at least 0.5 ms , the synaptic delay occurs before a
response is obtained in the postsynaptic neuron .
• Generation of EPSP and IPSP
• EPSP : Excitatory post synaptic potential The initial
depolarizing potential produced by a single stimulus to a
sensory nerve . This potential is not sufficient to generate an
action potential but it increases the excitability of the
neuron to other stimuli and is thus called an EPSP .

10. EPSP & IPSP
• The EPSP is produced by depolarization of the postsynaptic
membrane by the opening of Na+ or Ca++ channels in the
postsynaptic membrane .
• The depolarization produced by one synaptic knob is small
and it peaks 11.5ms after the stimulus and the
depolarizations produced by each of the active knobs
sumate .
• IPSP or Inhibitory postsynaptic potential is just the reverse
of an EPSP .
• IPSP are produced either by opening of Cl_ channels in which
negative charge moves inwards or opening of K+ channels or
by closure of Na+ or Ca++ channels .

11. TEMPORAL AND SPATIAL SUMMATION
• Temporal summation occurs if repeated afferent stimuli cause
new EPSP s before previous EPSPs have decayed .
• A longer time constant for the EPSP allows for a greater
opportunity for summation .
• Spatial summation occurs when activity is present in more than
one synaptic knob at the same time .
• Temporal and spatial summation is also seen in the case of IPSP .
• SLOW POSTSYNAPTIC POTENTIALS
• Slow EPSP and IPSP are seen in cases of autonomic ganglia ,
cardiac and smooth muscle and cortical neurons .These
postsynaptic potentials have a latency of 100 to 500ms & last
several seconds .These are due to K+ channels .

12. Generation of the action potential in the postsynaptic neuron
• In motor neurons , the portion of the cell with the lowest
threshhold for the production of a full fledged action
potential is the initial segment , the portion of the axon at
and just beyond the axon hillock.
• This part of the neuron is is either depolarized or
hyperpolarized electrotonically & is the first part of the
neuron to fire .The discharge is propagated in two directions
: down the axon & back into the soma.
• Retrograde firing into the soma has the value of wiping the
slate clean for subsequent renewal of the interplay of
excitatory and inhibitory activity on the cell.

13. Functions of Dendrites
1. Propagated action potentials are initiated in dendrites.
2. Dendritic spines appear, change & even disappear over
minutes & hours.
3. Changes in dendritic spines have been implicated in
motivation , learning and long term memory .

14. INHIBITION AND FACILITATION AT SYNAPSES
INHIBITION MAY BE PRESYNAPTIC OR POSTSYNAPTIC
POSTSYNAPTIC INHIBITION MAY BE OF TWO TYPES
DIRECT AND INDIRECT INHIBITION
DIRECT INHIBITION It is because of generation of IPSP
INDIRECT INHIBITION It is because of previous postsynaptic
neuronal discharge . Examples
1. Post synaptic cell may be refractory to excitation because it
has just fired
2. Less excitable due to after – hyperpolarization which is
quite prolonged in spinal neurons .

15. PRESYNAPTIC INHIBITION
• Seen in the case of AXOAXONAL SYNAPSES .
• 3 mechanisms for presynaptic inhibition
1. Activation of presynaptic receptors increases Cl_
conductance & this decreases the size of the action
potential reaching the excitatory ending .
2. This in turn reduces Ca++ entry and consequently the
amount of excitatory transmitter released .
3. Voltage gated K+ channels are opened and this leads to
efflux of K+ and reduced entry of Ca++.

16. TRANSMITTERS RESPOSIBLE FOR PRESYNAPTIC INHIBITION
1. GABA : Acting via GABA A receptors , GABA increases Cl_
conductance .
2. GABA : Acting via GABA B receptors , GABA increases K+
conductance and produces presynaptic inhibition in the spinal
cord . Example : Baclofen , a GABA B agonist is used to treat
spasticity of spinal cord injury and multiple sclerosis .
3. Gating of pain in the spinal cord in the dorsal horn due to
descending pathways that terminate on the afferent paths .
PRESYNAPTIC FACILITATION
Seen due to SEROTONIN : The K+ channels close due to increased
intraneuronal cAMP levels and the action potential is prolonged .

17. ORGANIZATION OF INHIBITORY SYSTEMS
1. AFFERENT INHIBITION : PRESYNAPTIC & POSTSYNAPTIC
2. NEGATIVE FEEDBACK INHIBITION : (post synaptic )
A) RENSHAW CELL INHIBITION : Seen in spinal motor neurons
B) Inhibition via recurrent collaterals seen in cerebral cortex
and limbic system.
3 . FEED FORWARD INHIBITION : Seen in cerebellum .
Stimulation of BASKET cells produces IPSP in the
PURKINJE cells , whereas both basket cells and purkinje
cells are excited by the same parallel fiber excitatory input .

18. SUMMATION AND OCCLUSION

22. SYNAPTIC PLASTICITY AND LEARNING
• Short and long term changes in synaptic
function as a result of the history of
discharge at a synapse , ie synaptic
conduction can be strengthened or
weakened as a result of past experience

23. Posttetanic Potentiation
• Production of enhanced postsynaptic potentials in
response to stimulation
• This enhancement lasts upto 60sec & occurs after a brief
tetanizing train of stimuli in the presynaptic neuron .
• There is an increase in Ca++ ions in presynaptic neuron
• Long Term Potentiation – seen in the Hippocampus
• Rapidly developing persistent enhancement of the
postsynaptic potential response to presynaptic
stimulation
• It resembles posttetanic potentiation , but is much more
prolonged & can last for days .
• There is an increase in Ca++ in postsynaptic neuron .

24. Habituation & Sensitization
• Habituation
• Repeated benign stimuli results in gradual disappearance
of the response .
• Inactivation of Ca ++ channels leads to decreased release
of neurotransmitter .
• Due to PRESYNAPTIC INHIBITION
• Sensitization
• Sensitization is the prolonged occurrence of augmented
postsynaptic responses after a stimulus to which an
animal has become habituated is paired once or several
times with a noxious stimulus .
• Due to serotonergic neurons & is due to PRESYNAPTIC
FACILITATION .

25. SUMMATION AND OCCLUSION
1. Neurons A and B converge on X and neuron B diverges on
neurons X and Y .
2. A stimulus applied to A or to B will set up an EPSP in X .
3. Spatial summation will take place if A and B are stimulated
at the same time . 2 areas of depolarization are created and
the resultant EPSP is twice as large and the membrane
potential may reach firing level .
4. In this case Y has not fired but its excitability has been
increased & it is easier for neuron C to fire Y during the
EPSP .Y is thus in the SUBLINIMAL FRINGE of X.
5. Neurons are in the sublinimal fringe if they are not in the
discharge zone but have their excitability increased .

26. OCCLUSION
• If action potentials are produced repeatedly in neuron B , X
and Y will discharge as a result of TEMPORAL SUMMATION
of the EPSPs that are produced .
• If C is stimulated repeatedly ,Y and Z will discharge .
• If B and C are fired repeatedly at the same time , X , Y and Z
will discharge .
• Thus, the response to stimulation of B and C together is not
as great as the sum of responses to stimulation of B and C
separately , because B and C both end on neuron Y .
• This decrease in expected response , due to presynaptic
fibers sharing postsynaptic neurons , is called OCCLUSION .

27. END PLATE POTENTIAL AND JUNCTIONAL POTENTIALS
• Binding of Acetyl choline at the neuromuscular junction of skeletal
muscle generates a local potential called the END PLATE
POTENTIAL .
• The current sink produced by this local potential depolarizes the
adjacent muscle membrane to its firing level .
• Action potentials are generated on either side of the end plate
and these in turn initiates muscle contraction .
• An average human end plate contains about 15-40 million Ach
receptors .Each n. impulse releases about 60 Ach vesicles & each
vesicle contains about 10,000 molecules of the neurotransmitter
.This amount is sufficient to activate about 10 times the no . of
Ach receptors required to produce a full end plate potential .

28. END PLATE POTENTIAL
• This large propagated response in the muscle obscures the
END PLATE POTENTIAL .
• If small doses of curare are administered then the AP is
reduced and only the END PLATE POTENTIAL at the muscle
end plate is recorded .
• This end plate potential decreases exponentially away from
the end plate and these potentials undergo TEMPORAL
SUMMATION .

29. JUNCTIONAL POTENTIALS
• In smooth muscles in which noradrenergic discharge is
excitatory , stimulation of the noradrenergic nerves
produces discrete partial depolarizations that look like small
end plate potentials and are called EXCITATORY JUNCTION
POTENTIALS .( EJP )
• These potentials summate with repeated stimuli .
• These potentials spread electrotonically .

30. REFLEX ARC AND REFLEX ACTION
• A reflex arc consists of a sensory neuron, generally one or
more neurons in the spinal cord or brain , and a motor
neuron .The reflex arc neurons confined to the CNS are
called interneurons .
• The sensory neuron receives information from a receptor
and conveys it to the CNS . Interneurons in the CNS process
the information & as a result a DECISION is taken .This
decision is conveyed to the motor neuron . The motor
neuron delivers the messages to the effector organ, which is
either a MUSCLE or a GLAND .

31. Features of a Reflex
1. Is an involuntary action
2. Is mediated by a reflex arc
3. Needs processing in the CNS below the level of the cerebral
cortex
4. Is inborn .( Only for classical reflexes not for condioned
reflex) .

32. From Genes To Behaviour
• Till about 20 years ago not much was known .
• Proteins involved in synthesis of neurotransmitters and
proteins involved in the signal transduction at synapses have
been identified . The genes coding for these proteins have
been studied for their loci and nucleotide sequence .
• Advanced imaging techniques have led us to understand the
relationship between neuronal networks and conscious
behaviour .

33. Artificial Neural Networks
• ANNs are computer models inspired by the structure and
behaviour of neurons .
• ANNs can learn and have the potential of replacing or atleast
assisting human beings in several tasks .
• An ANN can also be programmed to give the output in the
form of a particular diagnosis when the input consists of a
specific collection of findings .
• The input of atypical findings TRAINS ANN to take those also
into account when faced with a similar case in future . Thus ,
experience makes an ANN better at diagnosis .

34. Small Molecule Neurotransmitters
Synthesized in all parts of the neuron
Enzymes synthesizing the NT are present in the
cytoplasm throughout the neuron .
NT are packaged into vesicles only in the nerve
terminal .
Membranes that form the synaptic vesicles are
synthesized in the soma & transported by fast
axon transport to the nerve terminal where
they fuse with endosomes or the presynaptic
membrane .

35. • Small clear vesicles are released only at selected sites called
active sites on the presynaptic membrane
• Synaptic vesicles remain anchored to the cytoskeleton of the
nerve terminal by a group of proteins called synapsin .
• When synapsins are phosphorylated by activated kinases ,
the vesicles are freed from the cytoskeleton & move toward
the active zone .
• The activation of kinases is triggered by a rise in intracellular
Ca++ .
• Ca ++ influx occurs near the active zone & high Ca ++
concentration lasts < 1ms before it diffuses to other parts of
the axon terminal .
• After getting freed from the cytoskeleton the synaptic
vesicles are guided to their releasing site by a group of
proteins called Rab proteins .

36. • Binding of the synaptic vesicles to the presynaptic
membrane requires integral membrane proteins called the
SNARE proteins .
• SNARE proteins present in the vesicle membrane are called
vesicle –SNARE ( eg synaptobrevin ) .
• SNARE proteins present on the target membrane are called
target SNARE eg ( syntaxin ) .
• For exocytosis of synaptic vesicles to occur , the v- SNARE
must bind to the t-SNARE .
• TETANUS toxin inhibits synaptic transmission by degrading
the SNARE proteins .

37. GLUTAMATE
• Small molecule neurotransmitter , which is one of the main
amino acid neurotransmitter .
• Glutamate is synthesized by glial cells from either glucose (
via the Krebs cycle ) or from glutamine .
• Glutamate receptors are of two types
1. Ionotropic receptors –gate channels directly & action is
always excitatory
2. Metabotropic receptors –gate channels indirectly through
group II c hormonal mechanisms & actions may be either
excitation or inhibition .

38. IONOTROPIC GLUTAMATE RECEPTORS
1. AMPA
2. KAINATE
3. NMDA
AMPA & KAINATE receptors generate the large early
component of the EPSP .
NMDA receptor produces a small late component of the
EPSP .
The binding of Glutamate to NMDA receptor requires the
presence of glycine .
NMDA receptors are important in LONG TERM POTENTIATION
OF SYNAPSES .

39. GABA AMINO BUTYRIC ACID
• Main inhibitory transmitter of the CNS & is an amino acid NT
• It is abundant in the striatum & the reticular nuclei of the
thalamus .
• Thalamic GABA ergic neurons are important in sleep & EEG
synchronization & are also involved in the pathogenesis of
seizures .
• GABA is formed by decarboxylation of glutamate & is
degraded by transamination to succinic acid .
•

40. Glycine
• Inhibitory transmitter ( amino acid transmitter ) present
mainly in the spinal cord .
• Glycine is released by spinal interneurones that inhibit
antagonist muscles .
• Strychnine produces convulsions by acting as a competitive
antagonist of glycine at the postsynaptic inhibitory site .

41. Monoaminergic transmitters
1. Dopamine
2. Norepinephrine
3. Epinerphine
4. Serotonin
5. Histamine

42. Dopamine
• Cells of dopaminergic neurons are concentrated in the
substantia nigra, ventral tegmentun of the midbrain and the
posterior hypothalamus .
• The dopaminergic nigrostriatal pathway is important in the
regulation of posture & its degeneration causes Parkinsons
disease .
• The dopaminergic cells of the ventral tegmentum of the
midbrain give rise to two important projection pathways
that are thought to be involved in schizophrenia .
• The tubuloinfundibular tract extending from the arcuate
nucleus to the infundibulum of the hypothalamus secretes
dopamine ( prolactin inhibiting factor )

43. Dopamine ( contd )
• Dopaminergic neurons are also found in the olfactory bulb (
periglomerular cells ) , in the retina ( amacrine cells ), and in
the medullary chemoreceptor trigger zone .
• There are two main classes of postsynaptic dopamine
receptors , D1 and D2 .
• D2 receptor antagonists have been used as antiemetics and
prokinetics and as antipsychotics .
• Bromcriptine is a strong D2 agonist and weak D1 antagonist
and is used in galactorrhea for inhibiting prolactin secretion
& has been tried in the treatment of acromegaly and
Parkinsonism .

44. Norepinephrine
• Acts as the neurotransmitter at the postganglionic
sympathetic nerve endings .
• In the CNS , the noradrenergic system are organized into two
main systems
1. Locus ceruleus system originating from the pons
2. Lateral tegmentun system originating from the medulla .
Locus ceruleus neurones in the CNS play an important role in
arousal , motivation , pathogenesis of anxiety , melancholia
& depression .
Locus ceruleus neurones descending to the spinal cord are
important for modulating pain .

45. Noradrenalin ( contd )
• The lateral tegmentum system includes noradrenergic
neurones in the nucleus ambiguus , nucleus of tractus
solitarius and the dorsal motor nucleus of vagus .
• They project to the hypothalamus and control cardiovascular
and endocrine functions .
• Noradrenalin acts on alpha 1 and alpha 2 receptors .
• Alpha 1 receptors act only on the postsynaptic membrane
whereas alpha2 receptors are also present presynaptically
as inhibitory autoreceptors .When stimulated , these
receptors reduce the amount of neurotransmitter released
from the presynaptic terminal .

46. Epinephrine
• It is the neurotransmitter of the C1 group of cells , a cluster of
cells in the upper medulla that descend to the sympathetic
preganglionic cells in the spinal cord .
• Histamine
• Produced by the decarboxylation of histidine .
• Histaminergic neurones are present in the tuberomammilary
nucleus in the posterior lateral hypothalamus .
• They project to large areas of the cerebral cortex & spinal
cord and are important for the arousal response & other
visceral responses .

47. Serotonin
• 5-HT ( 5-Hydroxy tryptophan ) is produced from tryptophan by the
action of brain tryptophan hydroxylase .
• Serotonin promotes arousal , obsessive – compulsive acts and
overeating .
• Serotonergic neuron cells are located along the midline of the
brain stem in the raphe nuclei .
• The caudal part of the raphe nuclei sends descending projections
to the spinal dorsal horn where they modulate pain , muscle tone
and autonomic activity .
• The rostral part projects to the limbic system ,playing important
roles in cardiovascular regulation, thermoregulation , sleep-wake
cycle , food intake , sexual behaviour and emotions .

48. Serotonin
• Drugs blocking serotonin reuptake are used as
antidepressants in the treatment of melancholic depression .
• Serotonin agonists are used for treatment of migraine .
• There are 14 types of serotonin receptors .

49. Neuropeptides
• The 3 main endogenous peptides are
1. Enkephalins( leucine enkephalin & methionine enkephalin )
2. Beta –endorphin
3. Dynorphin
The 3 main receptors of opioid receptors are
1. Mu Agonist is Morphine . Antagonist is Naloxone
2. Delta
3. Kappa
The mu receptors are present in PAG area , ventral medulla and
substantia gelatinosa of the dorsal horn. All these are
important in regulation of pain .