NERVOUS SYSTEM VIVAS
Neurotransmitters and Neuromodulators
2011-2, 2006-2, 2004-2
What happens to acetylcholine when released into a synapse
- Binds to post-synaptic cholinergic receptors (nicotinic or muscarinic)
- Catabolism by (true/specific) acetylcholinesterase at the postsynaptic membrane
- Reuptake of choline
- No acetylcholine reuptake
- Diffusion -> catabolism by pseudocholinesterase in the circulation
Describe the differences between the two types of acetylcholine receptors.
- Divided on basis of pharmacological properties into muscarinic and nicotinic
Muscarinic
- Muscarinic–actions mimicked by muscarine and blocked by atropine
- Found in smooth muscle, glands and brain
- Serpentine receptors G-protein coupled to adenylyl cyclase and/or phospholipase
- 5 types (5 genes)
- M1 brain, M2 heart, M3 and 4 smooth muscle, M4 pancreas, M5 ?
Nicotinic
- Nicotinic–actions mimicked by nicotine
- 2 Types: neuromuscular junction vs autonomic ganglia and the central nervous system
- Ligand-gated sodium ion channels
- 5 subunits from 16 subunits (coded by 16 genes): alpha1-9, beta2-5, gamma, delta, epsilon
- Subunit structure differs location (gangli vs brain) & age (foetus vs adult)
Please describe the synthesis and release of acetylcholine at a nerve synapse. You may draw
a diagram
2009-1
What are the functions of serotonin
1. Regulation of the vomiting reflex
2. Regulation of mood
3. Control of respiration
4. Platelet aggregation and SMC contraction
5. Facilitate GI secretion and peristalsis
6. Regulation of circadian rhythm
What are the steps in the synthesis and catabolism of serotonin
1. Hydroxylation and decarboxylation of tryptophan -> serotonin
2. Released serotonin -> active reuptake mechanism
3. Inactivated by MAO -> 5HIAA (urinary metabolite)
2011-2, 2010-1, 2008-2, 2007-2, 2004-2
Outline the biosynthesis of adrenaline
1.
2.
3.
4.
Tyrosine -> DOPA (tyrosine hydroxylase)
DOPA -> dopamine (DOPA decarboxylase)
Dopamine -> noradrenaline (dopamine -hydroxylase)
Noradrenaline -> adrenaline (PNMT, phenylethalonamine methyltransferase, present only in
certain neurons and the adrenal medulla)
Notes:
- Noradrenaline and adrenaline are stored bound to ATP, with protein chromogranin A
- Stored in granulated vesicles
- Release after AP increases IC Ca2+ by exocytosis to synaptic cleft
What happens to noradrenaline after it is released into the synaptic cleft
Post synaptic or pre-synaptic binding to receptors
Terminated by:
1. Reuptake -> metabolised by MAO to inactive deaminated derivates (VMA) or recycled
2. Catabolised in the synaptic cleft by COMT (catechol-O-methyltransferase) to Normetanephrine
3. Diffusion
Which catecholamines act as neurotransmitters 2007-2
Noradrenaline, adrenaline and dopamine
What types of noradrenergic receptors are there 2004-2
1 – contraction of vascular SMC
2 – contraction of vascular SMC
1 – via heart and JG cells, increased force and rate + increases rennin
2 – Repiratory –> bronchial SMC relaxation, Skeletal muscle – vascular dilation
Adrenaline: 1 = 2, 1 = 2
Noradrenaline: 1 = 2, 1 >> 2
How do the effects of noradrenaline and adrenaline differ on the cardiovascular system 2004-2
BP: norad increase, adrenaline may decrease diastolic at low does via 2 effects, at higher increases
HR: both increase
CO: both increase
TPR: both increase
How do the effects of adrenaline differ with serum concentration 2004-2
Low concentrations – some beta effects, high concentrations alpha predominates, thus at low
concentration the diastolic BP may fall due to skeletal muscle blood vessel dilation (important effect
during exercise).
Properties of Sensory Receptors
2009-1
Describe the route followed by pain pathways from the periphery to the brain
-
Primary efferent w/ cell body in dorsal root
ganglia (or equiv in CNs)
Terminate on neurons in dorsal horn
A -> layers 1&5, C -> layers 1&2
2nd order neurons -> anterolateral system
aka lateral spinothalamic tract
To ventricular posterior nuclei (of thalamus)
Then to cerebral cortex
2009-1, 2006-2
Describe the characteristics of nerve fibers responsible for transmission of pain
Size
Conduction rate
Dorsal horn
Location
Type of pain
Neurotransmitter
Myelinated A delta fibers
2-5 m diameter
12-30 m/s
Lamina 1 and 5
Less in deep structures
Bright, sharp, localised
Glutamate
Unmyelinated C fibers
Smaller 0.4 – 1.2 m diameter
Slower 0.5 – 2m/s
Lamina 1 and 2
Dull, intense, diffuse
Substance P
What do you understand by the term referred pain
- Visceral pain felt at a somatic site, due to dermatomal rule (same embryologic segmental origin)
- May be due to same 2nd order neurons in dorsal horn -> thalamus (convergence-projection
theory)
- E.g. cardiac pain felt down the (L) arm
Reflexes
2010-2, 2006-1
Please describe a monosynaptic stretch reflex
1. Sensory efferent
- Ia from muscle spindle
- Cell body in DRG
- Enters via dorsal root
- Synapses w/
2. Motor afferent
- Exits via ventral root
- Contract the stretched muscle
Also:
3. Inverse stretch (autogenic inhibtion)
- Ib from Golgi tendon organ
- Inhibits motor neuron via interneuron
4. Reciprocal innervation
- Antogonistic muscles relax
- Inhibited by interneurons
Notes:
Reaction time: is the time from action to response (19-24ms for Knee Jerk)
Central delay: reaction time – nerve conduction time (0.6 – 0.9ms for Knee Jerk
How do the muscle spindles function 2005-1
- Muscle spindle and its reflex connections are involved in proprioception
- Intrafusal fibers are in parallel to the extrafusal fibers (regular contractile units of muscle)
- Ia fibers sensitive to velocity of change, the dynamic response
- The tonic activity of Ia and II fibers gives feedback on the steady state, the static response
- -motor neurons (static and dynamic) supply these to regulate the sensitivity
Notes:
Spastic tone due to hyperactive stretch reflexes
Hypotonic when -motor neuron discharge low, and hypertonic if -motor neuron discharge is high
Clasp knife effect: moderate stretch -> muscle contraction, strong stretch -> muscle relaxation
Clonus is from increased -motor neuron discharge (may be partly due to stretch vs inverse stretc
Sample Viva, 2009-1, 2006-2
Describe the withdrawal reflex
- Polysynaptic reflex arc consisting of sense organ afferent and efferent nerve and effector
- Noxious stimulus to skin or sub cut
- Response of flexor muscle contraction and extensor relaxation
- Result in withdrawal of limb from stimulus
- Cross extensor response: with a strong stimulus the contralateral limb will extend
What is meant by the term polysynaptic reflex
One or more interneurons and interposed between the afferent and efferent neurons
What are the effects of a polysynaptic reflex
- Prolonged effect as different times for stimulus to reach effector
- Reverberation circuit as some interneurons turn back on themselves further prolonging the effect
- Irradiation of the impulse up and down the spinal cord
- Recruitment of motor units
- Results in magnification of the response
What is meant by the term prepotency of the withdrawal reflex
- The withdrawal reflex will preempt the spinal pathways from other reflex activity occurring at the
same time
2011-1, 2007-2, 2005-2
What mechanisms does the body use to regulate temperature? PROMPT: What mechanisms
are activated by cold?
PROMPT: Are any voluntary?
1. Activated by cold: Shivering, Hunger, Increased voluntary activity, adrenaline and noradrenaline
secretion, decreased heat loss, cutaneous vasoconstriction, curling up, horripilation
2. Activated by heat: Increased heat loss, cutaneous vasodilation, sweating, increased respiration,
decreased metabolic heat production, anorexia, apathy & inertia
How are these temperature regulating mechanisms controlled?
- Reflex responses activated by cold controlled from posterior hypothalamus
- Those activated by warmth are controlled primarily from the anterior hypothalamus
2010-2, 2009-1
What factors are responsible for heat production and heat loss?
Heat Production
- Basic metabolic process
- Specific dynamic action of food
- Muscular activity
Heat is lost by
- Radiation and conduction 70%
- Vaporisation of sweat 27%
- Respiration 2%
- Urination and defaecation 1%
Describe the body’s adaptive response to a cold environment
- Activated by cold: Shivering, Hunger, Increased voluntary activity, adrenaline and noradrenaline
secretion, decreased heat loss, cutaneous vasoconstriction, curling up, horripilation
- Reflex responses activated by cold controlled from posterior hypothalamus
2005-2 How is fever generated
- Adjustment of thermoregulatory mechanisms as if the thermostat had been reset (above 37C)
- Thus temperature receptors signal that the actual temperature is below the new set point and
temperature raising mechanisms are activated -> shivering and chills
- Heat generation in cold environment, reduced heat loss in warm
- Pyrogenic stimuli (endotoxins, inflammation) -> cytokines from macrophages, monocytes and
Kupffer cells -> preoptic area of hypothalamus -> prostaglandins -> raise set point -> fever
2007-2
What is nystagmus (are there different types)
Characteristic jerky movement of the eye seen at the start and end of a period of rotation.
Types:
- Horizontal (eyes move in horizontal plane)
- Vertical (head tipped sideways in rotation)
- Rotatory (head tipped forward)
The direction of eye movement is identified by the direction of the quick component
Why does nystagmus occur
Reflex that maintains fixation on a stationary object while the body moves. Not initiated by visual
impulses.
- When rotation starts, the eyes move in opposite direction (vestibulo-occular reflex, VOR)
- When the limit of movement is reaches the eyes snap back to the new fixation point, and then
slowly in opposite direction
How is nystagmus mediated
- Slow component is initiated by impulses from the labyrinths
- Quick component is triggered by a centre in the brainstem
2007-1
What is the function of the reticular activating system?
1. Centres within network regulate respiratory, cardiovascular, vegetative and endocrine functions
2. Non-specific activation from any modality
3. Sends signals mostly to the thalamus
4. Increases cortical electrical activity
5. Increased consciousness, alert state, heightened sensory perception
Describe its location and structure?
1. Complex polysynaptic network
2. Mid ventral portion of medulla + midbrain
3. Converging sensory fibres from long tracts and cranial nerves