Neurones and Synapses Revision Lecture

By Anjitha Anilkumar- 4^th year medical student

AXA1383@student.bham.ac.uk

• The BIMS Pre-Clinical Revision Series is developed and run entirely by senior MBChB students who voluntarily give up their time to teach.

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• Teaching is to the best of tutors’ knowledge fully-factually correct, but please bear in mind that neither the tutor(s), nor BIMS accepts any responsibility for any inaccuracies in the material taught.

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• This teaching session is in no way affiliated with or endorsed by the medical school.

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DISCLAIMER

Pre-clinical Revision Series

Dec 2021

Lecture content:

• Structure of neurone and other cells of the nervous system
• Basic structure of the nervous system
• Cranial nerves
• Peripheral nervous system
• Membrane Potential
• Action Potential
• The NMJ
• Disorders of Motor Unit
• Reflexes
• Autonomic Nervous System
• Exam + Revision tips

Basic structure of a neurone

• Dendrites – receive incoming signals – excitatory/ inhibitory
• Cell body (Soma)- contains genetic info, maintains structure and is responsible for ATP generation. Has Nissl bodies
• Axons- conduct APs away from the cell body
• Myelin sheath – some neurons have myelin sheaths which act as insulation. Mainly neurons in CNS.

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Glial Cells

• Play supporting role

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CNS

• Microglia - related to macrophages and remove dead cells/ other debris
• Oligodendrocytes-produce myelin
• Astrocytes – lots of types with. Functions include formation and maintenance of the BBB- which reduces permeability of CNS to certain substances
• Ependymal cells, which line the ventricles of the brain and the central canal of the spinal cord, have hairlike cilia that beat to promote circulation of the cerebrospinal fluid found inside the ventricles and spinal canal.

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PNS:

• Satellite cells cover the cell bodies of neurons in PNS ganglia. Satellite glial cells are thought to support the function of the neurons and might act as a protective barrier, but their role is still not well-understood.
• Schwann cells – Myelin production

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Structure of the Nervous system

Topography and anatomy of the Brain and skull

• Dura mater = has a periosteal and a meningeal layer, between these will exist the dural venous sinuses (the venous drainage of the brain)
• Arachnoid mater = Translucent layer, below this layer is the CSF
• Pia mater – very delicate layer that attaches closely to the brain itself

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Vertebral Column and the spinal cord

Vertebrae

• 7 Cervical Vertebrae
• 12 Thoracic Vertebrae
• 5 Lumbar Vertebrae
• 5 Sacral Vertebrae – forms sacrum (fused )
• 4x Coccygeal Vertebrae – fused Coccyx

33 VERTABRAE

Spinal nerves

• 8 pairs of Cervical Spinal Nerves
• 12 pairs of Thoracic Spinal Nerves
• 5 pairs of Lumbar spinal nerves
• 5 pairs of sacral spinal nerves
• 1 pair of Coccygeal spinal nerves

31 PAIRS OF SPINAL NERVES

C1-C7 leave above their respective vertebrae, C8 leaves just below C7 Vertebrae. T1- S5 all leave below their respective vertebrae

Anatomy of the spinal cord

• Spinal cord terminates between L1/L2 as a structure called the conus medullaris

Remaining nerve roots come off the conus medullaris forming the Cauda equina

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Clinical correlation : Lumbar Puncture - diagnostic procedure which involves taking a sample of CSF

• insertion point of the needle between L3-L4 or L4-L5 vertebrae ; thus, the needle is inserted below the level of the spinal cord to avoid injust to the cord . It is inserted into the lumbar subarachnoid space.

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• CC: cauda equina syndrome – compression of the cauda equina -> loss of motor function, saddle anaesthesia and loss of bowel and bladder control!

Spinal Cord cross sectional anatomy

• Paired spinal nerves exit spinal cord via intervertebral foramina
• Each spinal nerve then divides into an ventral and a dorsal ramus.
• Each ramus contains a mix of sensory and motor fibres

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Key facts:

• Dorsal root ganglion = sensory neurone cell bodies
• Ventral horn contains cell bodies of lower motor neurones
• Lots of tracts in spinal cord – nerve fibres that carry similar information grouped together
• Lateral horns ( only T1- L2 )= contain cell bodies of sympathetic pre-ganglionic neurons

Cranial Nerves – important to know

• LR6 S04– CN VI Lateral Rectus, Superior Oblique – CN IV
• Cavernous sinus –oculomotor nerve (CN III), trochlear nerve (CN IV), ophthalmic nerve (V1), maxillary nerve (V2), abducens nerve (CN VI)- lesion in cavernous sinus can compress cranial nerves- i.e. pituitary tumour-> ophthalmoplegia, ptosis, and facial sensory loss due to involvement of adjacent cranial nerves.

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mneumonics :

CRANIAL NERVES: Oh Oh Oh to take a family vacation, go vegas after hours

MODALITY: Some say mary money but my brother days big brains matter more

Brachial plexus

Need to be able to draw this! + know which nerve roots make up each nerve

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• Nerve roots converge to form trunks ( posterior, anterior and middle trunk ) at base of neck
• Trunks divide into two branches each ( posterior triangle of neck )
• Anterior and posterior divisions combine again to form cords in axilla
• Cords give off branches which are 5 main brachial nerves ( NB there are others )

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CC: Erbs palsy- caused by trauma to Brachial plexus often during delivery of baby -> results in unilateral arm weakness and paralysis

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Lumbosacral plexus and sacral plexus

Sacral plexus =is formed by the anterior rami (divisions) of the sacral spinal nerves S1, S2, S3 and S4. It also receives contributions from the lumbar spinal nerves L4 and L5.

Lumbar plexus : L1-L4

Components of the peripheral nervous system

• Peripheral nerves are a mix of both motor and sensory neurones
• The endoneurium is a connective tissue layer surrounding the axons.
• The axons are arranged into bundles forming fascicles, which are surrounded by perineurium . The fascicles also have blood vessels between them .
• The whole nerve is surrounded by epineurium .

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Key terminology

• Nucleus = group of cell bodies in the brain /cerebral hemispheres
• Ganglion = group of cell bodies outside the CNS i.e. in the PNS
• Dermatome= region of skin supplied by a single spinal nerve
• Myotome = group of muscles innervated by a spinal nerve
• Plexus = group of intersecting nerves
• Cervical plexus (C1 – C4): innervates the diaphragm, shoulders and neck.
• Brachial plexus (C5 – T1): innervates the upper limbs.
• Lumbosacral plexus (L2 – S1): innervates the lower extremities.

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Physiology: The Action Potential

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1. Resting membrane potential = negative – determined primarily by K + movement
2. As membrane potential reaches threshold potential -> VG Na+ channels open – influx of Na+ ions
3. Depolarization = more Na+ channels open
4. Once Em of around +40 mv reached -> Na+ channels close and VG K= channels open-> K+ efflux out of cell -> REPOLARIZATION!
5. Hyperpolarization occurs because conductance of K + still high after resting membrane potential is reached
6. As repolarisation occurs, potassium channels close and sodium channels return to their activated but closed states.
7. The Na/K pump returns the membrane potential to its resting state.

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The Action Potential : important concepts

• The refractory period – ensures that another action potential isn’t generated
• Absolute refractory period – Na+ channels completely inactive so no new AP can be generated
• Relative refractive period – very negative membrane potential so more depolarisation needed to generate an AP
• Saltatory conduction occurs in myelinated neurones -> faster speed of conduction as depolarisation “jumps” between nodes of Ranvier

Physiology: The NMJ

1. Depolarisation of the motor neurone causes VG Ca2 + channels to open
2. Influx of Ca 2+ -> binds to synaptogamin- Vescicles containing Ach fuse with membrane ( exocytosis)
3. Ach diffuses across synaptic cleft and binds to the AchR receptors on the motor end plate of the myocyte
4. AchR contain pores for Na+, when Ach binds – these pores open = Na+ influx and depolarisation of the motor end plate-> more Na+ channels open – depolarisation and AP
5. AP travels through T tubule system

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Physiology : Muscle contraction- sliding filament theory

1. Depolarisation of the sarcolemma , spreads along the T tubules and enters the terminal cisternae in the sarcoplasmic reticulum( where Ca2+ ions are stored.)
2. This causes Ca2+ ions to be released into the sarcoplasm.
3. The Ca2+ ions bind to the troponin complex on the actin and this causes, tropomyosin to change conformation , leading to myosin head binding sites in the actin to be exposed .
4. The myosin head ( which has an ADP molecule attached to it) binds to the actin forming a cross bridge.
5. The ADP molecule detaches and this means that the msoin head undergoes a conformational change ( power stroke), which pulls the actin along .
6. Another molecule of ATP then binds and this causes the myosin head to detach from the actin.
7. ATP hydrolysis provides the energy for the recovery stroke, where the myosin returns to its original position but further don the actin.
8. This process is repeated several times during muscle contraction.

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Upper and lower motor neurone and signs

Key clinical applications: Disorders of the motor unit

Motor Nuerone Disease

• Degeneration of ventral horn cells – both upper and motor neurones affected
• Lots of sub types - ALS
• Progressive condition – resulting in weakness
• Resp failure leads to death ( innervation of diaphragm )
• UMN and LMN signs
• patient in 50s/60s

Gullian Barre syndrome

• Antibodies attacking myelin sheath / motor neurones
• Presents with symmetrical ascending paralysis, reduced reflxes . Loss of sensation
• LMN signs
• May start 4 weeks after viral infection

• Myasthenia Gravis
• Antibodies against Nicotinic Ach receptors in NMJ
• Leads to muscle weakness
• Progressively worse with activity and improves with rest
• Can cause respiratory depression
• Affects proximal muscles, and small muscles of head + neck and eyes
• Rx neostigmine- AchE inhibitor

Duchenne Muscular Dystrophy

• Genetic condition which causes progressive weakening of muscles
• Proximal muscle weakness
• X linked
• Children die early

Botulinum Toxin

• Very potent neurotoxins, produces paralysis by blocking presynaptic release (acetylcholine) at NMJ,
• with reversible chemical denervation of the muscle fibre, thereby inducing partial paralysis and atrophy
• produced by Clostridium botulinum
• botulism is often home-canned foods that are low in acid, such as fruits, vegetables and fish.
• Uses: Botox ( very small doses), treating some medical conditions such

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Autonomic nervous system

Divided into sympathetic and parasympathetic nervous systems

Controls visceral functions of body- homeostasis

Useful video for revision : https://www.youtube.com/watch?v=3a_aLsFvNWs

Parasympathetic nervous nervous system structure

• Terminal Ganglion – often in the wall of organ/ gland it innervates = short post ganglionic neurone
• Majority of nerves are a component of the Vagus nerve

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Sympathetic Nervous system structure

• Pre-ganglionic cell bodies in lateral horn of spinal cord from T1 –L2
• Ganglions in pre-vertebral and para vertebral ganglia Long post ganglionic fibres – they go along the nerve that supplies the end organ
• Adrenal medulla is directly supplied by the pre-ganglionic sympathetic fibre

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SUMMARY of PNS and ANS anatomy and neurotransmitters

Reflexes : Basic principles

Neural reflexes are rapid stereotyped involuntary reactions of the CNS to specific sensory input. ( the trigger)- protective mechanism.

5 components of a reflex:

1. Sensory receptor – detects stimulus – golgi tendon/ muscle spindle
2. Afferent- sensory nerve fibre
3. Integration – usually lamina IX of spinal cord
4. Efferent- motor neurons
5. Effector- muscle

Reflexes :Simple stretch reflex

Simple stretch Reflex ( Myotatic reflex ):

1. Muscle spindle detects stretch in quadriceps-> increase in sensory neurone activity
2. Increases activity of alpha motornuerones to quadriceps so they contract
3. Sensory neurone also synapses with interneurone , which is inhibitory- it releases inhibitory neurotransmitters which reduces the hamstring alpha motor neurone activity => relaxation of the hamstrings

 reflex arc that provides direct communication between sensory and motor neurons innervating the muscle

1. Proprioceptors detect muscle stretch -> increase in activity of sensory neurone
2. Increases in excitatory neurotransmitter activity in the at synapse and increases activity of alpha motor neurone
3. This leads to muscle contraction

= automatic regulation of skeletal muscle length and allows us to correct posture

Alpha motor neurones only release excitatory neurotransmitter

Reflexes :cross extensor reflex ( Inverse Myotatic )

• Contralateral reflex which means that if the body detects a stimulus on one side it can compensate on the other- e.g if you step on a pin
• Opposite of myotatic reflex because affected muscle group RELAXES rather than contracting
• branches of the afferent nerve fibres cross from the stimulated side of the body to the contralateral side of the spinal cord. There, they synapse with interneurons, which, in turn, excite or inhibit alpha motor neurons to the muscles of the contralateral limb.
• In the ipsilateral leg (the one which steps on the nail), the flexors contract and the extensors relax to lift the leg from the ground.
• On the contralateral side (the one that bears all the weight), the flexors relax and the extensors contract to stiffen the leg since it must suddenly support the entire weight of the body. At the same time, signals travel up the spinal cord and cause contraction of the contralateral muscles of the hip and abdomen to shift the body’s centre of gravity over the extended leg. 

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Golgi Tendon Reflex

• Stimulus is increased tension in the tendon – i.e a rock on the foot
• It connects to an excitatory interneuron- which releases excitatory neurotransmitters -> increases alpha motor neurone activity-> muscle contraction in opposite muscle to affected tendon
• Also connects to inhibitory interneuron -> inhibitory neurotransmitter released-> reduces alpha motor neurone activity ->muscle relaxation of affected muscle

Top Tips for MCQs & SAQs :

• Know the content of physiology lectures very well – Action potentials, NMJ etc all could be an SAQ
• Know common drugs and their effects – pharmacology is important
• Know which ions are responsible for changes in Membrane potentials, action potentials etc
• Cranial nerves are important – especially for clinical years
• Don’t forget the SDLs! The content can come up
• Rule out answers = process of elimination
• Nerve injury lecture is important
• For anatomy – draw stuff out – it really helps!
• Tables for pharmacology can be helpful
• Don’t stress, it’s going to be okay ☺

Not covered in this lecture

• Enteric nervous system
• Nerve damage and regenerative processes – know the sequence and definitions for types of nerve damage
• Neuro exam – geeky medics is helpful
• NAS pharma (Autonomic pharmacology lecture )– ( learn the drug groups, how they work and what effect they have and if they have clinical uses those as well – Table is helpful here ☺
• Anaesthetics ( review mechanism and examples ) and different modes of administration

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