Reciprocal regulation of presynaptic and postsynaptic proteins in bipolar spiral ganglion neurons by neurotrophins.
A unifying principle of sensory system organization is feature extraction by modality-specific neuronal maps in which arrays of neurons show systematically varied response properties and receptive fields. Only beginning to be understood, however, are the mechanisms by which these graded systems are established. In the peripheral auditory system, we have shown previously that the intrinsic firing features of spiral ganglion neurons are influenced by brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). We now show that is but a part of a coordinated package of neurotrophin actions that also includes effects on presynaptic and postsynaptic proteins, thus encompassing the input, transmission, and output functions of the spiral ganglion neurons. Using immunocytochemical methods, we determined that proteins targeted to opposite ends of the neuron were organized and regulated in a reciprocal manner. AMPA receptor subunits GluR2 and GluR3 were enriched in base neurons compared with their apex counterparts. This distribution pattern was enhanced by exposure to BDNF but reduced by NT-3. SNAP-25 and synaptophysin were distributed and regulated in the mirror image: enriched in the apex, enhanced by NT-3 and reduced by BDNF. Moreover, we used a novel coculture to identify potential endogenous sources of neurotrophins by showing that sensory receptors from different cochlear regions were capable of altering presynaptic and postsynaptic protein levels in these neurons. From these studies, we suggest that BDNF and NT-3, which are systematically distributed in complementary gradients, are responsible for orchestrating a comprehensive set of electrophysiological specializations along the frequency contour of the cochlea.
Flores-Otero
Jacqueline
J
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA.
Xue
Hui Zhong
HZ
Davis
Robin L
RL
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D008565:Membrane Proteins / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008808:Mice, Inbred CBA; D009414:Nerve Growth Factors / Q000502:physiology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D013136:Spiral Ganglion / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
D008565:Membrane Proteins; D009414:Nerve Growth Factors