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CNS Notes 2nd Part

1.Synaptic inhibitions & facilitation

1. Direct postsynaptic inhibition:
Stimulation of an afferent neuron inhibits an efferent neuron. The inhibition is direct and is
usually through an internuncial neuron. The neurotransmitter released is inhibitory in nature
Example: Golgi bottle neuron inhibition in reciprocal innervation and crossed extensor reflex
Mechanism : Stimulation of an afferent neuron from muscle spindle activates a golgi bottle
neuron that releases glycine which causes hyperpolarisation of the motor neuron
that supply to the antagonistic muscles.
2. Indirect postsynaptic inhibition:
Inhibition that occurs due to the effects of previous discharge from the postsynaptic neuron.
Mechanism: 2 ways:
i) Postsynaptic neuron remains refractory to the incoming stimuli because it has just fired and is
in the refractory period
ii) Neurons which initiate an excitatory impulse may inhibit themselves in a negative feedback
fashion.
Example: Renshaw cell inhibition:
The spinal motor neuron regularly gives recurrent collateral which synapses with an inhibitory
interneuron that terminates on the cell body of the same neuron. This inhibitory interneuron is
called Renshaw cell . This prevents excess discharge from the anterior horn cell
3. Presynaptic inhibition:
Inhibition occurs usually at the presynaptic terminals before the signal reaches the synapse.
Mostly modulatory in nature and usually axo-axonic type.
Example: Pain modulation in the spinal cord
Mechanism: A reflex response to stimulation of an afferent nerve is either abolished or
decreased by stimulating another afferent nerve .The second afferent nerve ending
synapses with presynaptic nerve terminal through an inhibitory interneuron. The
inhibitory neurotransmitter (Eg . GABA) released by this interneuron decreases
the depolarization of the presynaptic nerve terminals. Calcium entry into the
nerve terminals is decreased causing a decreased release of excitatory
neurotransmitter. This leads to a reduced response
4. Feedforward inhibition:
The afferent fibers first stimulate the efferent fibers and then inhibit the same fibers through
interneurons
Example: In cerebellum , the afferent fibers first stimulate the deep nuclei and then inhibit
them through purkinjee cells.
PRESYNAPTIC FACILITATION
A reflex response to stimulation of an afferent nerve is increased by stimulating another afferent
nerve.The second afferent nerve ending synapses with presynaptic nerve terminal through an
interneuron. The excitatory neurotransmitter (mostly serotonin) released by this interneuron
decreases the K+ current at presynaptic nerve terminals and increases the duration of
depolarization of the presynaptic nerve terminals. Calcium entry into the nerve terminals is
increased causing a increased release of excitatory neurotransmitter. This leads to an increased
response
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2. Properties of Receptors
a. Specificity:
Each type of receptor is highly specific for a particular stimulus for which it is designed and is
non responsive to normal intensities of other type of stimuli (e.g) Rods and cones respond to
normal intensities of light, but respond to only high intensity of touch.
b. Adequate stimulus:
The stimulus which can easily stimulate a receptor is the adequate stimulus for that receptor.
(e.g) Light is the adequate stimulus for rods & cones.
c. Labelled Line Principle:
The specificity of nerve fibers for transmitting only one modality of sensation is called labeled
line principle.
d. Doctrine of specific nerve energies:
Also called as Muller’s law. The sensation evoked by impulses generated in a receptor depends
in part upon the specific part of the brain they ultimately activate.
e. Law of projection:
When a stimulus is applied anywhere in the pathway of a sensation, the sensation is projected to
the receptors. (e.g) Phantom limb & Phantom pain
Phantom Limb: The non existing limb in an amputated person gives the sensation of pain &
proprioception as if it is existing.
Phantom pain: The pain sensation from the non existing limb of an amputated person can be
explained by law of projection ie., the stimulus applied anywhere in the pathway causes
projection of sensation to receptors)
Mechanism
Amputation → formation of neuromas → discharge of impulses by pressure or
Spontaneously→ sensation produced is projected to the place where the receptors were
presented.
f. Adaptation:
Reduction in sensitivity of receptors in the presence of a constant stimulus
• Phasic receptors: Fast adapting receptors (e.g) receptors for smell & pacinian corpuscles.
• Tonic receptors: Slow – adapting receptors (e.g) proprioceptors
• Receptors that do not adapt at all - Pain receptors (Nociceptors)
g. Intensity discrimination:
Weber Fechner Law: The magnitude of sensation felt is proportionate to the log of intensity of
stimulus
R=KSA
(R = Magnitude of sensation felt, S=intensity of stimulus, K & A = constants)
Intensity discrimination depends upon
• Number of receptors stimulated (spatial summation)
• Frequency of action potential reaching the cortex (Temporal summation)
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3. Sensory Tracts
1.Dorsal column pathway
Origin: From the dorsal column of spinal cord
Course:
I order neuron
• In the posterior nerve root
• After entering into spinal cord, ascend in the dorsal column of spinal cord
• Terminate in the nucleus gracilis & nucleus cuneatus of medulla
II order neuron
• From nucleus gracilis & nucleus cuneatus
• Cross to the opposite side (sensory decussation)
• Crossed fibers (called as inter nal arcuate fibers) upward in the medial lemniscus through pons &
mid brain.
• Terminate in the ventral postero lateral nucleus of thalamus (VPLN)
III order Neuron
• From VPLN of thalamus
• Pass through posterior limb of internal capsule
• Terminates in the SI & SII areas of cortex
• Sensations carried:
Fine touch, tactile localization, tactile discrimination, vibration, pressure, pain, conscious
proprioception & stereognosis.

2. Antero – lateral pathway

Origin: From the dorsal horn of spinal cord
Course:
I order neuron
• In the posterior nerve root
• After entering into spinal cord ascend up 1-3 segments or immediately end in nuclei of dorsal
horn.
II. Order neuron
• Starts from dorsal horn spinal cord
• Cross to opposite side in the anterior commissure
• Form 2 pathways
- Anterior spinothalamic tract
- Lateral spinothalamic tract
• Anterior spinothalamic tract runs in the anterior white column
• Lateral spinothalamic tract runs in the lateral white column of spinal cord
• Pass through medulla, pons, & mid brain
• Terminate in the VPLN of thalamus
III. Order neuron:
• from VPLN of thalamus
• pass through internal capsule
• terminate in the somatosensory cortex
Sensations carried:
Anterior spinothalamic tract – crude touch & pressure
Lateral spinothalamic tract – pain & temperature
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4. Regulation of Muscle Tone

Resistance of the muscle to stretch due to continuous state of tension in the muscle is called
muscle tone
Control of muscle tone:
• Muscle tone is purely a spinal segmental reflex.
• Produced by continuous, asynchronous, low frequency discharge from anterior horn motor
neurons
• This depends up on the activation of muscle spindle & stretch reflex.
Role of muscle Spindle
• Receptor organ present in the muscle
• Consists of infrafusal fibers (nuclear bag and nuclear chain fibers)
Sensory supply
▪ Group-Ia (annulospiral ending) – supply both fibers
▪ Group-II (Flower spray endings) – supply only nuclear chain fibers
Motor nerve supply
Gamma motor neuron
Muscle spindle participate in stretch reflex which play an important role in regulation of muscle tone
and posture
Role of stretch reflex
Reflex arc:
• Receptor - Muscle spindle
• Stimulus – Stretch
• Afferent – Group Ia & II fibers
• Center – Spinal Cord
• Efferent limb – motor nerve fiber ( α motor neuron)
• Response: Contraction of extra fusal fibers
Two types of reflexes
Dynamic stretch reflex: (phasic stretch reflex)
Activation of Group Ia fibers - contraction of agonist muscle and relaxation of antagonistic
muscle (helps is movement)
Tonic stretch reflex:
Activation of Group Ia & II fibers - continuous steady contraction of the antigravity muscles due
to asynchoronous discharge of motor units supplying the muscle
(necessary for maintaining muscle tone and posture)
Role of γ motor neurons on muscle tone
• γ motor neuron increases the sensitivity of muscle spindle to stretch
• increase inγ motor (gamma motor) neuron discharge increases muscle tone
• γ motor neuron discharge is increased in following conditions
noxious (painful) stimulation of skin
anxiety
Jendrassik phenomenon
Role of higher centers in regulation of muscle tone
Brainstem:
Brain stem reticular formation
Facilitatory reticulospinal tract(Pons) Inhibitory reticulospinal tract(Medulla)

Facilitates motor neuron discharge Inhibits motor neuron discharge

↑muscle tone ↓muscle tone

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Cerebellum: Increases muscle tone by

Facilitating motor cortex
Facilitating descending pathways
Cerebral cortex

Cerebral cortex Indirect pathway

Pyramidal tract Brain stem nuclei

Facilitates muscle tone Inhibits muscle tone

Applied
Hypotonia: ↓in muscle tone (lower motor neuron lesion & cerebellar lesion)
Hypertonia: ↑ in muscle tone (UMN lesion)
Spasticity – hypertonia only in antagonistic muscles (clasp knife rigidity)
(e.g) Hemiplegia due to pyramidal lesion
Rigidity: Hypertonia in both agonistic & antagonistic muscle
e.g Basal ganglia lesion – Parkinsonism
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5. VESTIBULAR APPARATUS
Components:
Vestibule (Utricle & Saccule)
Semicircular canals
Receptors:
Vestibule (otolithic organ) – Macula
Semicircular canals – Crista ampullaris
Stimulus
Vestibule - Linear acceleration
Semicircular canals – angular rotation
Activation of semi circular canals
Angular rotation

Movement of fluid in the semi circular canals

Bending of stereocilia towards the kinocilium

Entry of K+ into the hair cell

Depolarization

Calcium influx

Release of excitatory neurotransmitter (Glutamate)

On the opposite side:
Stereocilia move away from kinociliun

Hyperpolarization

Inhibition of Semicircular canals on opposite side

-Both of these cause relaxation of muscles on same side & contraction of muscles on opposite side
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Functions of Semicircular canals:

-helps to maintain equilibrium during rotational movements
-helps in visual fixation during angular rotation of head (vestibule-ocular reflex)

Otolith organ (vestibule) activation

Utricle responds to horizontal acceleration & Saccule responds to vertical acceleration
Functions of otolithic organ:
-gives information about static position of head
-respond to linear acceleration in different directions
Vestibular pathway

Vestibular apparatus

Vestibular division of VIII cranial nerve

Vestibular nucleus (Brain stem)

Vestibulo – cerebellar tract

Vermis of cerebellum

Cerebellar cortex Vestibular nucleus Vestibulospinal tract Spinal cord

6. Nuclei & Functions of Hypothalamus (important - regulation of water
balance, regulation of food intake & body temperature)
Nuclei of hypothalamus
1. Supra optic area: Includes supra optic, Suprachiasmatic, paraventricular & anterior nuclei
2. Preoptic area: Medial & lateral preoptic nuclei
3. Tuberal area: Ventromedial, dorsomedial, arcuate, lateral & posterior nucleus
4. Mammillary area: Medial & lateral mamillary, pre & supramamillary nuclei.
Functions of Hypothalamus
a) Regulation of food intake

Ventromedial Nucleus Lateral Nucleus

(Satiety center) (Feeding Center)

Inhibits feeding center Hunger

↑Food intake ↓food intake

b) Regulation of water intake

Tonicity of body fluid ECF volume

Osmoreceptors Baroreceptors

Thirst center Thirst center Angiotensin II

↑Water intake ↑Water intake Subfornical organ

Thirst center
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c) Regulation of body Temperature

Pre optic nucleus of anterior hypothalamus (heat loss center) → Sweating and vasodilatation
Posterior hypothalamus (heat gain center) → Shivering & vasoconstriction
d) Control of ANS
(Acts as a head ganglion of ANS)

Stimulation of anterior Stimulation of posterior

Hypothalamus Hypothalamus

↑HR, BP & HCL secretion ↓HR & BP, Pupillary dilatation,

Micturition, erection of penis sweating & piloerection
(Parasympathetic effects) (sympathetic effects)
e) Control of Pituitary
Hypothalamus Supra optic & paraventricular nuclei of hypothalamus

Releasing &
inhibitory
Hormones

Anterior pituitary Posterior pituitary

Trophic hormones ADH Oxytocin

Target endocrine gland Water re-absorption Milk secretion

In kidney in mammary glands
&
contraction of uterus
f) Role in circadian rhythm
-Hypothalamus play a role in influencing the changes in body functions tuned to the day and night
cycle (circadian rhythm)

Retina

Optic tract

Suprachiasmatic nucleus of hypothalamus

Pineal gland

Melatonin

Day & night variations

g) Role in emotions:
Hypothalamus is a part of papez circuit which is responsible for emotional behavior.
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h) Role in stress
Hypothalamus helps to protect the body from damaging effects of stress
Stress

Cerebral cortex & Limbic system

Sympathetic
Nervous system Hypothalamus Adrenal cortex Adrenal medulla

Glucocorticoids Catecholamines
i) Role in sleep wakeful cycle
Hypothalmus has 2 sleep centers
- diencephalic sleep zone
- basal fore brain sleep zone
j) Role in sexual behavior
Hypothalamic areas (Preoptic & anterior hypothalamus) are responsible for sexual behavior like
mating, attracting the opposite sex etc.
k) Reward & punishment
Ventromedial nucleus – Reward center
Posterior & lateral nucleus - Punishment center
Important Functions:
a) Role of Hypothalamus in food intake
Food intake is controlled by 2 nuclei. They are
i) Ventromedial nucleus (VMN) – Satiety center
Inhibits the feedings center
Produces satiety (satisfaction) after taking food
Destruction of VMN - Hyperphagia & obesity
Stimulation of VMN - Hypophagia (↓food intake)
ii) Lateral nucleus (LN) – Feeding center
Stimulaters appetite
Produces hunger
Destruction of LN – aphagia & starvation
Stimulation of LN – Hyperphagia (↑ food intake)
Hypothesis about food intake
1. Glucostatic Hypothesis
Hyperglycemia in blood → ↓VMN activity → ↓ food intake
Hypoglycemia in blood →↑VMN activity →↑ food intake
2. Lipostatic Hypothesis:
Adipose tissue secretes “leptin” → inhibits hypothalaminus →↓ food intake
3. Gut peptide Hypothesis
Presence of food in GI tract → release of intestinal peptides (GRP, glucagon, somatostatin &
CCK) → acts on brain → satiety
4. Thermostatic Hypothesis
↓Body temperature →↑ food intake
↑Body temperature →↓ food intake
b) Role of Hypothalamus in regulation of water intake
• Mainly involves ‘thirst center
• Dorsal or lateral hypothalamus acts as thirst center
• Water intake mainly depends upon the stimulation of thirst center
• Thirst center is stimulated in 2 conditions
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a) in the increased tonicity of the body fluid

b) in the decreased ECF volume
a) Increase in the tonicity of body fluid

Stimulation of osmoreceptors

Stimulation of thirst center

Water intake
b) Decrease in ECF volume

Baroreceptors

Stimulation of Thirst center Angiotensi II

↑Water intake Subfornical organ

Thirst center
C. Regulation of Body Temperature
• Hypothalamus is called as ‘biological thermostat as it controls the body temperature constant
• Involves preoptic region of the anterior hypothalamus & posterior hypothalamus
Preoptic nucleus of anterior hypothalamus -- heat loss center
Posterior hypothalamus -- heat gain center
Stimulation of the centers occurs through 2 mechanisms
a) Cutaneous thermoreceptors
b) Blood flowing through hypothalamus
(-mediated through serotonergic pathway)
Stimulation of anterior hypothalamus Stimulation of posterior hypothalamus

Vasodilatation, sweating Vasoconstriction

& panting Shivering & Piloerection
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7. THALAMUS
Specific sensory nuclei
• ventrobasal group (VPLN & VPMN)
• medial & lateral geniculate bodies
Non specific sensory nuclei
• midline & intralaminar nuclei
Nuclei concerned with efferent control
• ventrolateral & ventro Anterior Nuclei
Nuclei concerned with higher functions
• dorsomedial, dorsolateral, pulvinar, posterolateral & Anterior nucleus
Functions
a) Sensory Relay Center:
sensory relay center for the following sensations:
• Tactile sensation
• vibration
• pressure
• conscious proprioception
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• stereognosis
• sexual sensation
• visual sensation (LGB)
b) Centre for crude sensations:
• Perceives the crude touch, pain & Temperature Sensation
c) Integrator of motor signals
• controls the smooth, slow and coordinated movements by its connections with cerebellum basal
ganglia & cerebral cortex.
d) Role in memory & emotions
• Being a part of Papez circuit, it influences recent memory & emotions.
Papez circuit
Mammillary body of Hypothalamus

Anterior Nucleus Hippocampus

Of thalamus

Cingulate gyrus
e) Role in sleep wakefulness cycle
• influences sleep wakefulness cycle.
• stimulation causes alertness of animal which facilitates learning process
• produces the B-rhythm of EEG
• Non-specific Nuclei are responsible for them
• Connections involved. (Reticulo thalamo cortical & Cortico thalamo reticular)
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8. Withdrawl reflex
•Refers to the withdrawal of body parts by flexion of limbs when a painful (noxious)
stimulus is applied.
• -It is a polysynaptic reflex
Receptors: Nociceptors
Afferent Limb: Type III & IV somatic afferents
Center: Spinal Cord
Efferent fibers: Somatomotor neuron supplying the flexor muscles of same side and
extensor muscles of opposite side.
Response:
Mild stimulus- flexion of limb of same side and extension of limb of opposite side.
Stronger stimulus - response in all four limbs.
(Reason: a) Irradiation of impulse, b) Recruitment of more motor units)
Special features:
• Withdrawl reflex is a protective reflex (protects the tissue from damage)
• Pre potent (stops all other spinal reflexes temporarily)
• Shows local sign ie., response depends upon the location of the stimulus
• Stronger stimulus causes wide spread and prolonged response
(Causes: After discharge due to involvement of many interneuronal pathways
& reverberatory circuits in the spinal cord)
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9. Modulation of Pain/ Endogenous Pain Relief System
Analgesia [inhibition of pain]:
1. Gate control theory
2. Endogenous pain relief from PAG(Peri Aqueductal Grey matter) & NRM / Central Pain
suppressing Mechanisms
3. By release of Endogenous opioid peptides (Enkephalins & Endorphins)
Gate control theory of pain
- the posterior or dorsal horn acts as a Gate for pain
- pain impulses in the spinal cord can be modified or gated by other afferent impulses [touch
,pressure vibration] that enter the spinal cord
- Large myelinated A fibers interact with small unmyelinated C fibers via
inhibitory cells of the Substatia gelatinosa of the spinal cord
- Stimulation of C fibers inhibits SG cells & favours passage of impulses along
the pathway of pain in the spinal cord.
- Stimulation of large ‘A’ fibers increases SG activity & block impulse
transmission to nerve cells concerned with pain-
(inhibit transmission of pain from the ‘C’ fibers to Spinothalamic tract.-
presynaptic inhibition)
- pain inhibiting opioids also act at the level of gate
Endogenous pain relief from PAG/central pain suppressing mechanism
- Descending pathways arise from Periaqueductal gray matter [surrounding aqueduct of Sylvius]
[release Encephalin] → Descend & connect with Nucleus raphe magnus of medulla →release
of Serotonin → posterior horn cells of spinal cord → inhibits the release of substance “P” from
the pain fibers
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Opioid peptides:
oEnkephalins—
▪ Met enkephalins ,Leu enkephalins
o Endorphins-
▪ Beta endorphins, & Dynorphins
o Similar in action to Morphine
o Present in PAG (peri aqueductal gray matter),NRM( nucleus raphae
magnus),periventricular
o areas, posterior horn cells, GITract & Hypothalamus
o Endogenous morphine - ENDORPHINE
◼ Two sites of action:
-Terminals of pain fibers (receptors) & decrease the response of the receptors
to nociceptive stimuli
-At spinal level – binds to opioid receptors & decreases the release of
substance - P
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10. REFERRED PAIN

Visceral pain instead of being felt at the site of the viscera is frequently felt at some
distance,on somatic structures. This is called referred pain
Eg: Appendicitis pain at the umbilicus
Cardiac pain at the inner aspect of left arm
Cholecystitis at the tip of the shoulder.
Theories of referred pain: (mechanism of referred pain)
1. Convergence theory: Fibers carrying pain- both from the viscus & the
corresponding dermatome (somatic structures) converge on the same pathway to
the cortex
2. Facilitation theory: The visceral pain produces a subliminal fringe effect on the
Substantia Gelatinosa Rolando [SGR] cells which receive somatic pain nerves

CONVERGENCE THEORY
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11. Inverse Stretch Reflex

Refers to relaxation of muscle in response to a strong stretch.
Also called as lengthening reaction or clasp knife reflex.
Receptors: Golgi tendon organ
Afferent fibers: Group Ib fibers
Center: Corresponding spinal segment
Efferent fibers: α motor neuron to the corresponding muscle
Response: Inhibition of α motor neuron by the inhibitory interneuron and relaxation of the
corresponding muscle.
Functions:
-Monitors the force generated in the muscle
-reflex is called autogenic inhibition
-monitors muscle tension and prevents rupture of muscle
-along with stretch reflex maintains optimal motor responses for postural adjustments
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12. Reciprocal innervations
-refers to the contraction of agonist muscles and relaxations of the antagonistic muscles in response to
the stimulation of an afferent nerve
Circuit:
Afferent fibers: Group Ia & II fibers
Center: spinal card
Efferent fibers: motor neurons supplying agonist and antagonistic muscle
Response: contraction of agonist muscle and relaxation of antagonistic muscle
(relaxation is due to stimulation of an inhibitory interneuron)
Importance:
-essential for normal physiological movements like walking
-useful in eliciting crossed extensor reflex between two upper limbs

13. Crossed extensor reflex

- stimulation of a limb causes flexion of limb on same side and extension of opposite limb.
- Mediated through interneurons
-Take part in withdrawal reflex