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23 Cards in this Set
- Front
- Back
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In axon growth, what do the growth cones do? |
- Growth cones drag growing axons from the neuronal cell body to their targets in the embryo - it functions much like the leading lamella of a moving cell, except that the nucleus gets left behind - it is supplied by axonal transport, with sufficient reserves to keep going for a while after amputation (enough nutrients are present for axon to grow even if disrupted) |
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Axonal growth cone |
- sensory motile tip of growing axons - guides axon growth by moving in response to chemical cues present in developing embryo, crawling through the developing nervous system and dragging a growing axon, but not the neuron's cell body, to wire up with one another |
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What do the growth cones contain? |
- it contains receptors, which bind chemical guidance cues to elicit chemotropic response - this chemotaxis guided by attractive and repulsive cues in the extracellular environment, can be diffused or static |
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Floor plate |
special group of neruons on the central canal and resides on it |
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Chemoattractive growth cone guidance (in embryonic spinal cord) |
Floor plate secretes a diffusible molecule called NERTIN which diffuses through the tissue forming a concentration gradient that attracts axons to cross from one side of the cord to the other (signalling is recognised) -> pulls the axon from dorsal horn area and goes down towards the floor plate and crosses over forming a commissure (junction/joint) |
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In mouse that do not have nertin... |
- transverse image of embryonic spinal cord in mouse is observed - wild type (normal mouse) have a clear circular shape formed by the stained axons, but nertin negative (knocked out) have no nertin released from floor plate so commissure does not form |
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Nasal retina fibres |
- retina close by the nose - contains retina ganglion which picks up light and crosses over though optic chiasm, but temporal fibres don't |
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Chemorepulsive guidance (at optic chiasm) |
- Temporal fibres do not cross because a strip of ventral midline cells express Ephrin B2 ligand on their surfaces, which repels the in growing temporal fibre - Temporal growth cones have EphB2 receptors specific for Ephrin B2 ligand - Upon binding of ligand, Eph receptor signals intracellularly (phosphorylation of receptor) to redirect the growth cone |
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Basic guidelines of NMJ formation |
1. Outgrowth and migration
2. Myoblast fusion (myoblast growth cone approaches newly formed myotube and forms a morphologically unspecialized but functional contact) 3. Synaptogenesis (schwann cells enters allowing multiple axons to converge on a single site - all axons but one is eliminated, and survivor matures) |
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Clutch hypothesis |
- Mitchison and Kirschner 1988 - They stated that filopodial protrusion/extention occurs by actin assembly, when an actin filament is fixed with respect to the substrate (i.e clutch is engaged) - When clutch is disengaged, retrograde flow occurs to direct the rearward movement of F-actin by treadmilling and by the action of molecular motors - This allows for filopodial retraction to occur when retrograde flow rate exceeds the actin assembly rate |
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AChR in embryos -> adults |
- embryonic AChR: 2 alpha, beta, delta, gamma - once matured, gamma is replaced with upsilon (E) subunit - such change in receptor makes faster and higher conductance |
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AChR clustering |
- In both developing axon and the myotube can create ACh and AChR respectively (independently from one another) - AChR is distributed diffusely on the surface of newly formed myotubes - Developing axons release AGRIN, which binds to basal lamina and causes the clustering of AChRs - release of neuregulin by the developing axons up-regulates the expression of AChR genes in nuclei that lie directly beneath the nerve terminals |
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Mutation in axons |
- agrin is not expressed thus dies at birth due to grossly perturbed NMIs |
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Lab techniques to determine position of AChRs |
- labelling the receptors with bungarotoxin shows the most of the recruited AChR are newly synthesized so, pre-existing AChR have not moved into the end plate |
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Rapsyn |
Intracellular peripheral membrane protein required for agrin mediated Musk activation |
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MuSK |
muscle specific kinase (tyrosine kinase) linking various intracellular proteins causing ACh receptors to cluster post-synaptically and stimulate maturation |
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AChR genes in extrasynaptic regions |
- transcription of AChR genes are down-regulated in nuclei in extrasynaptic regions - because: during development, electrical activity evoked by synaptic transmission represses ACh gene expression in nuclei in non-synaptic regions of the embryonic muscle, leading to lower density of ACh receptors in these regions |
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How do NMJ accomodate so many receptors |
- junctional folds are formed - they have complex cytoskeletal structure to facilitate their many AChRs - unfolded stretches support neglible quantities of AChRs |
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Synaptic pruning |
- activity dependent - hypothetically: synapse strong enough to produce an AP will trigger myonuclei directly across from the axon to release synaptotrophis that will strengthen and maintain well-established synapses - Synaptic strengthening: not conferred upon the weaker synapses |
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Roles of schwann cells in NMJ formation |
they begin to produce myelin for just one of the fibres and, with the withdrawal of polyneural innervation to one end plate, begin to form a myelinated cap over the entire neuromuscular junction |
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Axonal CREB |
- CREB (cAMP response element binding protein) is synthesized in response to NGF - CREB is transported to cell body where it is essential for phosphorylation of cell body CREB and so neurons survive (Lonze and ginty 2002) - they have epigenetic effects, so may be possible for the axon to modify neuronal gene expression |
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In nerve damage |
- motor axons regenerate and form new NMJ - nearly all of the new synapses form at the original synaptic sites - regenerating axons differentiate into nerve terminals when they contact original synaptic basal lamina - Thus components of synaptic basal lamina accounts for selective re-innervation of synaptic sites and trigger the differentiation of growth cones into nerve terminals |
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When nerves don't regenerate but muscles do... |
- the expression of AChR on the regenerated myofibres surface is concentrated in the region of the synaptic basal laminal - this shows that components of basal lamina are sufficient to direct the localization of ACh receptors on the muscle membrane |
