neurotrophic factors
1. NGF can support the growth of axons even though other parts of the neuron, such as the cell body, are starved of NGF. 2. NGF can support the survival of neurons when it is only applied to axons, indicating that NGF is capable of sending a "retrograde signal"
2 things that compartmentalized tissue cultures showed
1- very rapid 2- does not cause inflammation 3- no cell remnants left behind
3 facts about apoptosis
BDNF
Merkel disk receptors, involved in somatosensation, require _____, therefore express TrkB
NT3
Muscle spindles are associated with which neurotrophic factor
- A potent survival factor for sensory and sympathetic neurons. - if blocked, neurons will undergo apoptosis. this was the first growth factor to be identified.
NGF
TrkA
NGF uses which receptor
TrkC
NT-3 uses which receptor
TrkB
NT-4/5 uses which receptor
1. match the number of afferents to the available amount of target 2. regulate the degree of innervation of individual afferents and their postsynaptic contacts 3. modulate the growth and shape of axonal and dendritic projections 4. promote differentiation of immature neurons to their mature phenotype
Neurotrophic factors regulate 4 key processes in the formation of neural circuits
- Receptor tyrosine kinases - responsible for the survival and growth-promotion effects of the neurotrophins.
Trks
The target is required for the survival of the innervating motor neurons.
conclusion from the limb ablation experiment
There is competition for a limited amount of target AND cell death is a normal part of neural development.
conclusion from the limb addition experiment
BDNF and TrkB (neurotrophin and receptor)
ex: merkel disk neurons require two things, otherwise will die off
-BDNF is regulated by neuron activity. -Active areas in the brain produce more BDNF, which promotes formation of more synapses in that area.
explain BDNFs role in developing brain circuits
NT4/5
hair follicles are associated with which neurotrophic factor
they are made in limited amounts
how do neurotrophic factors establish competition between neurons
dynein
how does the ligand+receptor complex travel from distal axon to cell body?
1. loss of function in TrkA receptor, or 2. no NGF present either one means no development of nociceptors
if can't feel pain and can't sweat, but somatosensation is normal, what are 2 possible problems?
1. NGF binds to trkA 2. stabilized NGF+TrkA (ligand-receptor complex) is the retrograde neurotrophin signal 3. NGF+TrkA reaches cell nucleus to regulate gene expression and promote survival
mechanism of retrograde neurotrophin signaling
NGF
neurons that form free nerve endings (nociception) in the skin require _____ for survival, therefore express TrkA
GDNF Neurturin Artemin Persephin
what are the 4 GDNF receptor factors
NGF. NT3. NT4/5. BDNF
what are the 4 neurotrophins
ret receptor
what do all the GDNF factors signal through and promote survival and growth of?
1. support the growth and survival of neurons 2. they activate signal transduction pathways that induce protein and energy synthesis, and inhibit apoptotic pathways.
what do neurotrophic factors do? how?
the receptor that is expressed
what is the main determinant of the responsiveness of neurons to neurotrophins?
TNF (Not RTK)
what kind of receptor is p75?
all
which neurotrophin binds to the p75 receptor?
NGF
which neurotrophin does a sympathetic ganglia respond to?
NT3
which neurotrophin does the nodose ganglia respond to?
NGF, BDNF, NT3
which neurotrophins does a DRG respond to?
promotes the growth of dendrites in neurons of the cerebral cortex.
BDNF (brain derived neurotrophic factor)
TrkB
BDNF uses which receptor
