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Neurons Flashcards

1
Q

What embryological structure gives rise to the CNS?

A

Neural tube

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2
Q

What forms the neural tube?

A

Notochord induces overlying ectoderm to form neural tissue

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3
Q

What gives rise to the PNS?

A

Neural crest

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4
Q

What is neurulation?

A

Folding of neural plate to form closed neural tube

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5
Q

Give two examples of neural tube defects

A
  1. Spina bifida

2. Anencephaly

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6
Q

What establishes cell identity along the A-P axis of the neural tube?

A

Hox genes

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7
Q

What is the Hox code?

A

Unique pattern of Hox gene expression in cells of the neural tube

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8
Q

What do Hox genes encode?

A

Transcription factor proteins that bind DNA and regulate transcription of other genes

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9
Q

What are signalling centres?

A

Act as organisers by secreting growth factors

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10
Q

What does the midbrain/hindbrain boundary (isthmus) secrete?

A

FGF8

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11
Q

What does FGF8 do?

A

Induces special fates in adjacent neural tissue dorsally

Midbrain tectum anteriorly

Cerebellum posteriorly

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12
Q

What does ventral neural tissue adjacent to isthmus generate?

A
  1. Dopamine neurons of substantia nigra

2. Cranial nerve motor neurons III + IV

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13
Q

How does the notochord induce the neural tube floorplate?

A

Secretion of Sonic hedgehog (Shh)

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14
Q

What patterns the dorsal-ventral axis of the spinal cord?

A

The floorplate of the neural tube

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15
Q

What do the highest concentrations of Shh induce?

A

Floorplate

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16
Q

What do lower concentrations of Shh induce?

A
  1. Motor neurons

2. Suppress dorsal spinal cord neuronal phenotypes

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17
Q

What is the ventricular zone?

A

Where multipotent stem cells of the neural tube divide

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18
Q

What do stem cells of the neural tube form?

A
  1. Neurons

2. Radial glia

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19
Q

What is the role of radial glia?

A

Provide a scaffold for neuroblast migration

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20
Q

What is the fate of neuronal stem cells?

A
  1. Disappear - differentiate into astrocytes

2. Persist in olfactory bulb and dentate gyrus cells of hippocampus

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21
Q

When does production of neurons cease?

A

Infancy

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22
Q

What do neural crest cells generate?

A
  1. Dorsal root ganglia
  2. Autonomic ganglia
  3. Schwann cells
  4. Adrenal medulla chromaffin cells
  5. Enteric neurons
  6. Melanocytes
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23
Q

What gives rise to head mesenchyme and skeleton?

A

Neural crest cells

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24
Q

What is a growth cone?

A

Guides axon to the right place

Navigates using actin/myosin interaction to promote cell motility

Heads forwards as long as it has a suitably adhesive substrate and is not deflected

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25
What regulates growth cone progress?
1. Adhesion | 2. Signalling
26
What are neurotroPic factors?
Attractive Promote chemotaxis of growth cone
27
What are neurotroPHic factors?
Nourishing Promote survival and sprouting of neurons
28
Give two examples of diffusible/attractive factors
1. Nerve growth factor (NGF) | 2. Netrin
29
What is NGF?
Nerve growth factor Member of neurotrophin family
30
Give two examples of diffusible/repellent factors
1. Semaphorins | 2. Slit
31
What are contact/attractive factors?
Cell adhesion molecules
32
What do growth cone CAMs adhere to?
1. Large proteins in extracellular matrix 2. Same CAM on neighbouring cell 3. Another CAM on neighbouring cell
33
What is homophilic adhesion?
Growth cone CAMs adhering to same CAM on neighbouring cell
34
What is heterophilic adhesion?
Growth cone CAMs adhering to different CAM on neighbouring cell
35
What do CAMs connect to intracellularly?
1. Cytoskeleton | 2. Cytoplasmic signal transducers eg. tyrosine kinases
36
What large proteins in extracellular matrix might CAMs adhere to?
1. Laminin | 2. Fibronectin
37
Give three examples of contact/repellent factors
1. Semaphorins 2. Ephrins 3. Some proteoglycans
38
What attracts spinal cord axons to the floorplate?
Netrin
39
Where do commissural axons come from?
Dorsal neurons
40
What do the commissural axons give rise to once they decussate at the floorplate?
Future spinothalamic tract
41
What do floorplate molecules direct growth cones to do whilst crossing?
1. Turn rostrally 2. Become insensitive to netrin 3. Become more sensitive to inhibition so that they don't cross back 4. Change CAM expression
42
What CAM change leads to fasciculation of commissural axons?
TAG-1 replaced by L1-CAM
43
What causes temporal retina axons to avoid posterior tectal membranes?
Gradient of contact-repellent ephrin ligand
44
What causes generic synapse formation?
Synapse-specific adhesion molecules on axons and dendrites Recruit specific pre- and post-synaptic protein complexes
45
What causes activity-dependent selection of synapses?
1. Long-term potentiation | 2. Long-term depression
46
How can the final number of neurons be changed?
1. Increased by transplanting extra limb | 2. Decreased by amputation
47
What is the result of loss of NGF in the embryo?
1. Loss of all sympathetic neurons | 2. Loss of many sensory ganglion neurons
48
What is the receptor for target-derived NGF?
TrkA at the axon terminal
49
What is the role of target-derived NGF?
1. Prevents expression of target cell death programme (apoptosis) 2. Maintains neuron survival 3. Promotes axon sprouting 4. Chemotactic
50
What are the insulin-like neurotrophins?
1. NGF 2. BDNF 3. NT3 4. NT4
51
What is GDNF?
Supports dopamine neurons of substantia nigra and some motor neurons
52
What is Hebb's rule?
Long term potentiation 'Fire together, wire together' Selection of correlated input
53
Where is long term potentiation found?
Hippocampus
54
Which receptors are involved in long-term potentiation?
NMDA receptors
55
What occurs to the distal axon stump following crush/cut?
Wallerian degeneration Both axon and myelin degenerate
56
What occurs to the nerve cell body following nerve damage?
It survives Reacts by re-expressing genes for axonal growth
57
What condition is required for proximal stump axons to regenerate?
Endoneurial tube of living Schwann cells present to guide them
58
What is a neuroma?
Local swelling that axons sprout into when the break is greater than 1cm May produce intractable pain
59
What is the maximum distance CNS axons can regenerate?
1mm
60
Why is the mature CNS environment non-permissive for axon growth?
1. ECM lacks growth-promoting molecules such as laminin 2. Oligodendrocytes and CNS myelin express proteins that inhibit axon growth such as Nogo 3. Astrocytes proliferate and produce growth-inhibitory chondroitin sulphate proteoglycans in brain ECM
61
What is Nogo?
Neutralising antibody that reduces oligodendrocyte inhibition
62
What is a glial scar?
Densely interwoven tissue formed by astrocytes following brain injury Causes growing axons to stop
63
What is NT3?
Neurotrophic factor for corticospinal neurons
64
How does ischaemic injury, such as stroke, damage neurons?
Excitotoxic Increased intracellular calcium damages/kills neurons
65
What are neural stem cells?
Multipotent cells that divide to self-renew and produce differentiating cells with various phenotypes
66
What are progenitor cells?
Cells that can divide but only produce cells of defined cell types
67
Where are neural stem cells located in the fetal brain?
Ventricular and subventricular zone
68
What are dentate gyrus granule cells involved in?
1. Learning | 2. Antidepressant drug action
69
Where do new neurons for olfactory bulb come from?
Subventricular zone and anterior horn of lateral ventricle
70
How are induced pluripotent stem cells obtained?
From differentiated cell types Transfection with genes for four stem cell transcription factors Provide patient-specific source of stem cells

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