The Journal of Neuroscience, August 15, 2000, 20(16):6267-6275
AMPA Receptor-Mediated, Calcium-Dependent CREB Phosphorylation in
a Subpopulation of Auditory Neurons Surviving Activity Deprivation
Lance
Zirpel,
Mary A.
Janowiak,
Charles A.
Veltri, and
Thomas N.
Parks
Department of Neurobiology and Anatomy, University of Utah School
of Medicine, Salt Lake City, Utah 84132-0001
Although dependence on afferent synaptic activity has been shown
for central neurons in every sensory system, the mechanisms of afferent
maintenance of target sensory neurons are not understood. Neurons in
the cochlear nucleus (CN) require afferent activity for maintenance and
survival. One of the earliest changes seen after activity deprivation
is an increase in intracellular calcium that leads to the death of 30%
of the neuronal population. Sixty minutes after deafferentation, the
surviving neurons show increased phosphorylation of the transcription
factor calcium/cAMP response element-binding protein (CREB). CREB
phosphorylation in activity-deprived CN neurons is dependent on
increased intracellular calcium resulting from influx through
AMPA receptors and is mediated by
calcium/calmodulin-dependent kinases and protein kinase A. We
conclude that in CN neurons, the deafferentation-induced increase in
calcium activates at least two kinase pathways that phosphorylate CREB
in surviving neurons. We hypothesize that this phosphorylation results
in the transcription of genes containing the calcium/cAMP response
element within their promoter regions, and these genes code for
proteins that allow the neurons to compensate for their hypercalcemic,
activity-deprived state.
Key words:
chick nucleus magnocellularis; activity-dependent; deafferentation; calcium homeostasis; propidium iodide; neuronal
survival; cell death; mouse AVCN
Copyright © 2000 Society for Neuroscience 0270-6474/00/20166267-09$05.00/0
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