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Anterograde stimulation (synaptic)
NM
Stim
Comm.
Auditory
nerve
3 H-proline
labeling
A
Retrograde stimulation (action potentials only)
Stim
3 H-proline
labeling
B
FIGURE 7.33 Synaptic activity regulates postsynaptic protein synthesis in chick auditory brainstem. A.
Brain slices containing the chick nucleus magnocellularis (NM) and its auditory nerve afferents were incubated
in an oxygenated solution containing 3 H-proline. Synaptic transmission in one NM was elicited by electri-
cally stimulating the auditory nerve. When the tissue was processed for autoradiography, it was found that
synaptically stimulated NM neurons incorporated far more proline (black dots) into newly synthesized pro-
teins compared to the control side. B. When the axons of NM neurons were stimulated at the commissure,
evoking a retrograde action potential in the cell body, protein synthesis was not maintained. (Adapted from
Hyson and Rubel, 1989)
work through similar cytoplasmic effectors. Interest-
ingly, the activity of nonsynaptic NMDA receptors
suppresses CREB phosphorylation and increases
apoptosis. In the chick cochlear nucleus, deafferenta-
tion initially results in calcium elevation, and it is this
calcium that appears to be responsible for killing 30%
of the neurons. However, the 70% of neurons that
survive may well depend on CREB, which is phos-
phorylated within one hour of deafferentation. The
source of calcium is from AMPA-type glutamate recep-
tors. The survival pathway may be quite similar to that
discussed for neurotrophins: Within 6 hours of deaf-
ferentation, the expression of an anti-apoptotic gene,
bcl-2 —known to be regulated by CREB—has increased
(Zirpel et al., 2000; Wilkinson et al., 2002).
Although it is not yet clear how a localized calcium
entry biases a neuron toward life or death, it may have
something to do with the cytoplasmic localization of
calcium sensors. For example, when a calcium-
dependent kinase (CaMKII) becomes autophosphory-
lated, it becomes associated with a specific NMDA
receptor subunit (Strack and Colbran, 1998).
It is possible that afferents release trophic factors,
along with neurotransmitters, during development.
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