neurotrophins Flashcards
which subunit is the active component of NGF?
beta subunit
describe what happens to NGF and its receptor when NGF is administered to a growth cone
- NGF binds to receptor
2. NGF and its receptor is internalised and retrogradely transported from growth cone to cell body
what is the high affinity receptor that NGF binds to?
TrkA
what is the low affinity receptor that NGF binds to?
p75
what is a pro-protein?
a protein that is activated once it is cleaved
which Trk receptor does BDNF bind to?
TrkB
which animals have no neurotrophins at all?
drosophila
c. elegans
list some cytokines that act as survival factors in the nervous system
hepatocyte growth factor
ciliary neurotrophic factor
macrophage stimulating protein
why does co-ordinated electrical activity in the pre-synapse and post-synapse lead to survival of the synapse?
the more active the synapse is, the more neurotrophin it takes up via membrane recycling
merkel cells
mechanoreceptors sensing touch
are innervated but do not need innervation to differentiate
DEFINE: post-synaptic density
accumulation of cytoskeleton and membrane associated proteins at the post-synaptic membrane
what is the post-synaptic target of the auditory nerve endbulb?
spherical bushy cell
what are the changes occurring when a growth cone turns into a pre-synapse?
- filopodia retraction - growth cone senses where the target cell is
- formation of tight junctions between growth cone and post-synaptic neuron
- addition of membrane and ECM to post-synaptic membrane
- pre-synaptic vesicles, post-synaptic density, receptors and dense ECM accumulate in the cleft
cat visual cortex
- at post natal day 10, more axons are being made + synaptic density increases
cat is opening its eyes for the first time
retina receives sensory input —> drives synapse formation
what dictates where synapses form?
- site availability –> cell body blocked by astrocytes
- growth cone communicating with target. e.g. if target expresses ACh receptors on membrane, growth cone begins to synthesis ACh + electrical activity occurs
- pre-prepared sites on post-synaptic membrane for growth cone. made by laying down ECM (cadherins and other adhesion molecules)
Gephrin protein
binds to glutamate receptor
causes clustering of glutamate receptors in the post synaptic membrane
inject anti-sense RNA –> loss of clustering, glutamate receptors are more diffuse due to no gephrin
what is ARIA?
protein released by motor neurons
causes increase in AChR subunit ε mRNA
when synapses mature, ARIA causes replacement of gamma subunit for ε subunit to form mature junctional AChR –> causes synthesis of mature AChR
neuregulin family
what do neuregulins do?
pattern developing brain
upregulate NMDA receptors in developing cerebellum
what induces receptor clustering?
neural agrin in basal lamina
what is the mechanism of agrin?
- neural agrin in the basal lamina binds to MUSK on muscle cell membrane
- MUSK associates with rapsyn
- mediated by complex = RATL and MASC - rapsyn brings together ACh receptors, laminin, alpha-dystraglycan, beta-dystraglycan in a plaque
describe how synaptic connections are refined by focusing
initially, multiple climbing fibres innervate one purkinje cell
synapse between one climbing fibre and purkinje cell selectively strengthened because of highest activity in climbing fibre + competition
selected climbing fibre translocates from soma to dendrite
other weaker climbing fibres on the soma are eliminated
what are some morphological features of synapse specialisation?
- vesicles containing neurotransmitters at pre-synaptic membrane
- narrow cleft - filled with ECM, receptors + tight junctions
- thickened post-synaptic membrane due to post-synaptic density
Ig domains
confer stickiness
experiment showing the role of agrin
- make neuromuscular junction with chick nerve innervating rat muscle. antibody binding neural agrin stops clustering. antibody binding muscle agrin does not stop clustering.
- remove agrin mRNA from hippocampus using antisense mRNA - synapses decrease
what is the hebbian synapse?
coordinated activity of a pre-synaptic terminal and post-synaptic membrane strengthens the synaptic connections between them
describe an experiment showing that the neuron’s choice of neurotransmitter depends on the environment
transplant quail sympathetic neuron (adrenergic) into cholinergic site in chick
sympathetic neuron synthesises ACh instead of NA
parasympathetic neruon synthesises NA instead of ACh
describe an experiment showing that the target affects the neuron’s choice of neurotransmitter
transplant foot pad tissue (normally cholinergic innervation) into a site that is adrenergic
nerve innervating foot pat synthesises ACh
what are silent synapses?
intact, non-functional synapses where a pre-synaptic action potential fails to evoke a post-synaptic signal
