B6W6 - Spinal Cord Pathway

Front 1

What is the cause of cauda equina syndrome?
What are the main features?

Back 1

Cauda equina syndrome is due to compression of most descending nerve roots in lumbar spinal canal (<L2). Usually caused by central disc prolapse. Rare: tumour, epidural metastases.

Features:
- saddle area loss (S2-S5 dermatome)
- distended tonic bladder
- Constipation (reduced rectal tone & incontinence)
- Weak sacral myotomes.

Front 2

What are the 2 types of condition lead to block of neuron?

Back 2

- Demyelination = conduction block
- Axonal destruction

Front 3

What is the electromyography (EMG) reading at rest of: conduction block and axonal destruction?

Back 3

EMG -> record muscle activity with conscious contraction - recorded during rest and light voluntary activity

At rest:
Conduction block = silence
Axonal destruction = fibrillation potential
Fibrillation potential is because the denervated muscle is no longer electrically silent at rest.

Front 4

What is the EMG reading at mild effort of: conduction block and axonal destruction?

Back 4

Both conduction block and axonal destruction = motor unit dropout

Front 5

What is the nerve conduction / velocity study results for conduction block and axonal destruction?

Back 5

Conduction block = corrected with distal stimuli
Axonal destruction = Not corrected with distal stimuli

Front 6

What is the characteristics of the spinal cord at the level of:
- Cervical
- Thoracic

Back 6

Cervical:
- both funiculus cuneatus and gracilis in the dorsal column
- largest white matter to grey matter ratio

Thoracic:
- contains only funiculus gracilis
- lateral horn (T1 - L2) - sympathetic innervation of the body

Front 7

What are the characteristics of the spinal cord at the level of:
- Lumbar
- Sacral

Back 7

Lumbar:
- Lateral horn - only up to L2
- Largest ventral horn

Sacral:
- Smallest white matter to grey matter ratio
- Ventral horn
- Small funiculus gracilis

Front 8

For the following spinal cord nucleus, state the spinal cord level where it can be find, laminae on the spinal cord and function.

Clarke's Nucleus

Back 8

Clarke's Nucleus:

SC lvl - T1 - L2
Laminae - VII
Function - posterior spinocerebellar tract cells

Front 9

For the following spinal cord nucleus, state the spinal cord level where it can be find, laminae on the spinal cord and function.

Intermediolateral nuclei (column)

Back 9

Intermediolateral nuclei.

SC lvl - T1 - L3
Laminae - VII
Function - preganglionic sympathetic neurons

Front 10

For the following spinal cord nucleus, state the spinal cord level where it can be find, laminae on the spinal cord and function.

Sacral parasympathetic nucleus

Back 10

Sacral parasympathetic nucleus.

SC Lvl - S2 - S4
Laminae - VII
Function - preganglionic parasympathetic neurons -> pelvic viscera

Front 11

Describe what’s happening on the ‘stretch’ reflex in terms of information transmission and muscle activation.

Back 11

Stretch reflex:
o Tapping patellar tendon => activates muscle spindle (detects stretch or length; located on the muscle belly)) => 1a (A alpha) afferent fibre => synapse on alpha motor neurons at the same level of the SC => contracting extensor muscle => passive stretch.
o The stretch information carried by 1a afferent fibres is also passed onto interneurons of the intermediate grey => inhibits alpha motor neurons of the opposite (hamstring - flexor) muscle => reciprocal inhibition.

Front 12

Describe the process of ‘clasp-knife’ response. What type of motor lesion is associated with this condition

Back 12

‘Clasp-knife’ response:
o Golgi Tendon Organs (GTO) sense tension in the muscle tendons => information transmission by fast ‘1b’ afferent fibres.
o 1b fibres synapse on both excitatory and inhibitory neurons in the intermediate grey – which synapse on the same motor neuron (? alpha motor neuron) => muscle contraction can be either facilitated, or inhibited.
o When there is damage to descending pathways, muscle resistance is greatly increased – passive flexion of a joint may be at first strongly resisted (facilitation of extensors) but may slowly then completely disappeared (inhibition of extensor).
 Characteristic of upper motor neuron lesion.

Front 13

Describe the process of withdrawal reflex.

Back 13

Withdrawal reflex - in response to pain

2 components:
 Flexor reflex
• Cutaneous receptor => involve many levels of SC => requires coordination of extensor and flexor responses, including reciprocal inhibition.
 Crossed extensor reflex
• Simultaneous and opposite pattern of activity in the other limb, to prepare to support the body’s weight.

Front 14

Label the following diagram of SC pathway

Back 14

Diagram

Front 15

What are the 2 types of nociceptor neurons?

Back 15

o A-delta - lightly myelinated, large, fast
o C fibre - non myelinated, small, slow

Front 16

What receptor responsible in detecting hot temp? Cold? Touch?

Back 16

Cutaneous receptor:
o Hot – Organ of Ruffini
o Cold – Bulbs of Krause
 The extreme of both hot and cold are perceived as ‘pain’ by these receptors – the concept of parallel processing
o Touch – Meisner’s corpuscles (fine touch; superficial location / epidermis) & Pacinian corpuscle (deep pressure; deeper location / dermis)

Front 17

What are the 3 types of neuron (based on structure) and give an example for each?

Back 17

o Pseudounipolar e.g. sensory neuron
o Bipolar e.g. bipolar cells of the retina
o Multipolar e.g. motor neuron

Front 18

Name 5 sensory tracts and fill in the details.

Back 18

Sensory tracts.

Front 19

Where do fibres of dorsal column and spinothalamic tract cross over?

Back 19

Level of cross over:
- Dorsal column - Just before the midbrain.
- Spinothalamic tract - at the level of spinal cord

Front 20

The thalamus is divided by internal lamina into 4 groups of nuclei. What are they?

Back 20

o Anterior group
o Lateral group
o Medial group
o Intralaminar nuclei

Front 21

What is the name of the nucleus where the somatosensory pathways projects in the thalamus?

What are the sub divisions of the nucleus? What are the input and output of each subdivision?

Back 21

VP (Ventral posterior) nucleus.

Front 22

From the VP nucleus of the thalamus, they projected to the somatosensory cortex. Where is this?

Back 22

Post central gyrus of the cerebrum.
o The primary somatosensory cortex is also called ‘S1’ area.
S1 is mapped according to the body plan, it is somatotopic. More sensitive regions occupy more cortex than less sensitive ones.

Front 23

In the 2 somatosensory tract, the information is ‘mapped’. In which part of the pathway does it integrated?

Back 23

VP nucleus of the thalamus.

Front 24

Describe the steps involved in the process of transmission of NT.

Back 24

Transmission process:
o NT molecules are packed into membranous vesicle and docked at the presynaptic terminal
o Depolarisation of presynaptic membrane causes Vg-Ca2+ to open and allows Ca2+ into the terminal.
o Increase in intracellular [Ca2+] leads to fusion of vesicles with presynaptic membrane (exocytosis)
o NT release into extracellular space and diffuse passively to post-synaptic membrane across the synaptic cleft.
o NT bind to the receptors in the post-synaptic membrane: ionotropic or metabotropic receptors; causes ion influx leading to depolarisation of the post synaptic membrane.

Front 25

What are the 3 mechanisms by which NT can be cleared from the synaptic cleft?

Back 25

NT in the synaptic cleft is cleared away by continuous diffusion, enzymatic degradation or active uptake into cells.

Front 26

What are the 5 steps of classical transmission (Katz’ postulate – to establish new NT)?

Back 26

5 steps of classical transmission (SSRBT):
o Synthesis – presynaptic
o Storage – presynaptic
o Release – into the synaptic cleft via exocytosis
o Binding to receptor – post-synaptic; to iono or metabotropic receptors
o Termination

Front 27

Describe the mechanism of action of ionotropic and metabotropic receptors. How are they different from each other?

Back 27

• Ionotropic receptor = ligand gated ion channel
o Direct opening of ion channel upon ligand binding
• Metabotropic receptor = G-protein Coupled Receptors (GPCR)
o Ligand binding to receptor => activated GPCR => release of subunits => acts directly on ion channel or via activation of effector protein

Front 28

Name the ionotropic and metabotropic glutamate receptors.

Back 28

Ionotropic:
• AMPA, NMDA, KA

Metabotropic
• mGluR 1-8

Front 29

What are the possible fates of Glu in the synaptic cleft?

Back 29

• Bind to (R) post-synaptically
• Reuptake into pre-synaptic terminal via EAA
• Diffused and taken up by glial cells by Glu transporters.

Front 30

What is the characteristic of all ionotropic Glu (R)s?

Back 30

All Glu (Rs) are heteromultimer of 4 subunits.

Front 31

NMDA (R) – Is it slow or fast? What is NMDA-R permeable to? What is its association with [Mg2+]? What is required for channel opening?Antagonists?

Back 31

NMDA R – slow
• Once Glu binds => release Mg2+ from channel => Ca2+, Na+ influx & K+ efflux. Mg2+ topically inhibits ion movement. Block by high [Mg2+]. Required [gly] for channel opening.
• Antagonist: ketamine.

Front 32

AMPA R – Slow or fast? What is it permeable to?

Back 32

AMPA R – fast
• Permeable to: Na+, K+, Ca2+

Front 33

mGluR 1-8
 What are the roles of mGluR?

Back 33

Act as autoreceptors on the pre-synaptic membrane to inhibit NT release.

Front 34

Describe the process of glutamate cycle (SSRBT).

Back 34

• Synthesis – in glial cells by glutamate synthase converting uptake glutamate to glutamine (Gln).
• Storage – uptake by neuron in the form of Gln which deamidated by PAG (phosphate-activated glutaminase) to glutamate and stored in the vesicle.
• Release
• Binding to receptors
• Termination

Front 35

Describe the GABA cycle. How is it deactivated?

Back 35

GABA cycle:

• Synthesis – in glia cells, glutamate synthase converts Glu to Gln. Uptake by pre-synaptic cells and converted by glutaminase to Gln and by GAD (Glutamate decarboxylase) to GABA.
• Storage
• Release - exocytosis
• Binding to receptors
• Termination

Deactivation by:
• Diffusion
• Uptake into glia
• Reuptake as glutamine

Front 36

Name GABA ionotropic and metabtropic receptors.

Back 36

Ionotropic receptors: GABA-A, GABA-C.

Metabotropic receptors: GABA-B

Front 37

What is the action of GABA-A? What other molecule that binds to this receptor at different site?

Back 37

GABAA role: fast inhibitory signalling in CNS. Used as sleeping pills.

Benzodiazepines bind to GABAA at different binding sites.

Front 38

What is the action of activated GABA-B? Name 2 agonists to GABA-B.

Back 38

GABA-B:
• Coupled to GIRK (G-protein Coupled Inward Rectifier) – leads to K+ efflux.
• Action: inhibition in CNS postsynaptically and presynaptic inhibition.
• 2 agonists: GABA & baclofen (to treat spinal spasticity).

Front 39

What is the definition of Central Pattern Generator (CPG)? Give one example of proof of this concept.

Back 39

Central pattern generator = neural network that can endogenously (i.e. without rhythmic sensory or central input) produce rhythmic patterned outputs – inhibition/stimulation of certain groups of cells.

Proof:
o Stimulation can initiate locomotion in spinal patients (paraplegic)

Front 40

What is Brown-sequard syndrome? What is it characterised by?

Back 40

It is a hemi lesion of the spinal cord at the level of lumbar vertebtrae, affecting the lower limbs.

It is characterised by:
- Loss of vibration and position sense of the affected side (dorsal column)
- Weakness of the lesion side (anterolateral motor pathway)
- Loss of pain and temperature sensation (spinothalamic pathway)

Front 41

For the following spinal cord syndrome, describe the location of the lesion and symptoms associated with it.

Posterior cord syndrome.

Back 41

Posterior cord syndrome = lesion of the posterior spinal cord at the cervical level.

Symptom:
- loss of vibration and position sense (dorsal column) of both sides of the body from neck down.

Front 42

For the following spinal cord syndrome, describe the location of the lesion and symptoms associated with it.

Anterior cord syndrome.

Back 42

Anterior cord syndrome = lesion of the anterior spinal cord at the level of spinal cord.

Symptom:
- loss of motor function and sense of pain and temperature from the neck down.

Front 43

For the following spinal cord syndrome, describe the location of the lesion and symptoms associated with it.

Transverse cord lesion.

Back 43

Transverse cord lesion = lesion spanning the whole spinal cord at the lumbar level.

Symptom:
- loss of motor function, vibration and position sense, and pain and temperature bilaterally from waist down.

Front 44

Where does the corticospinal originate from?

Back 44

1/3 M1, 1/3 M2 (area 6), 1/3 S1 (area 3, 1, 2)
- Both frontal and parietal cortex.

Front 45

From what type of cells in the cortex does corticospinal tract originate from?

Back 45

Pyramidal cells in layer V of the cortex.

Front 46

Describe the pathway of corticospinal tract.

Back 46

Corticospinal tract:

Cereberal cortex (M1, SMA, PMC, S1) -> corona radiata -> internal capsule -> cerebral peduncles -> enter pyramids on the ventral aspect of medulla -> 90% cross over at the pyramidal decussation (lateral corticospinal tract), 10% do not cross (ventral corticospinal tract) - most of these cross before entering the ventral horn.

Front 47

What is the function of corticospinal tract?

Back 47

Provide input to motor neurons that innervate skeletal muscles, esp flexors.

Front 48

Describe the corticobulbar fibres pathway.

Back 48

Head and face regions of the motor areas (M1) -> corona radiata -> genu of internal capsule -> cerebral peduncles (medial to the corticospinal) -> synapse bilaterally on the motor nuclei of cranial nerves (except for CN VII (facial) - only contralaterally for lower CN VII)+ cells of the reticular formation.

Front 49

What is the characteristics of the following? Is it glutamatergic or GABAergic?
- Corticospinal tract
- Corticobulbar tracts

Back 49

- Corticospinal tract - Glutamatergic
- Corticobulbar fibre - Glutamatergic

Front 50

Describe what happens in the left upper motor neuron lesion of CN VII (facial CN).

Back 50

Weakness of the lower left face muscle but spared left forehead - forehead is innervated bilaterally by both left and right CN VII nuclei.

Front 51

Describe what happens in the right lower motor neuron lesion of CN VII (facial CN).

Back 51

Weakness of the left side of the face; both forehead and the rest of the face.

Front 52

Name the tracts that are included in the bulbospinal tract and the cells of origin of each tract.

Back 52

Bulbospinal tract = brainstem to spinal cord

a) Rubrospinal tract: red nucleus
b) Reticulo-spinal: reticular formation
c) Tecto-spinal: tectum (superior and inferior colliculus)
d) Vestibulospinal: vestibulocochlear nerve (CN III)

Front 53

Describe the rubrospinal tract pathway. Where does it cross over? Where does it end?

Back 53

Somatotopic M1 -> red nucleus -> cross over in midbrain or medulla -> lateral medulla -> terminate in SC intermediate grey (Rexed's V - VIII) -> flexor groups.

Front 54

Where does reticulo spinal tract originate from? What are its functions?

Back 54

Origin: peri-aqueductal grey.
Functions:
- mediating motor function
- mediating autonomic functions
- modulating pain impulses

Front 55

There are 2 reticulospinal tracts: medial (pontine) and lateral (medullary). What are their functions?

Back 55

Lateral and medial pathways have opposing effects.
Lateral: facilitates extensors, maintain posture.
Medial: liberates antigravity mm from reflex control

Front 56

Describe the pathway of the tecto-spinal tract.
What are its function?

Back 56

Deep layers of the superior colliculus -> cross midline in the midbrain -> descend in C/L central medulla close to medial meniscus -> terminate in the C/L inetermediate grey (lamina VI and VII) in the cervical levels.

Function: orientation reflexes of the head, especially towards auditory and somatosensory stimuli.

Front 57

What is the origin of the vestibulospinal tract? What are the pathways to both lateral and medial vestibular nuclei? Innervation?

Back 57

Nuclei of the CN VIII pons.
Descend bilaterally through medial longitudinal fasciculus to lower medulla (spinal accessory nucleus) and upper cervical spinal cord to innervate muscles controlling head position and orientation reflexes.
Fibres from the lateral nucleus projects to all level of the SC.

Innervate extensor groups and help maintain posture and balance.