UC San Diego

Neuronal circuits must balance adaptation to new developmental stages and a changing environment with the stability necessary to maintain percepts, memories and learned competencies for long periods of time. Studies of the role activity plays in neuronal survival, morphology and connectivity illustrate these two opposing forces. In the highly dynamic olfactory bulb (OB), which integrates newly born neurons throughout adulthood, we compare the roles of first and second order neuronal signaling on the survival and morphology of several types of OB interneurons. We find that loss of first-order OSN signaling leads to a subtle decrease in OB area due to elevated cell death. Loss of second order MT cell signaling, on the other hand, leads to a more dramatic loss of area and decreased density of several interneuron populations. Surprisingly, MT cells are unaffected by OSN signaling blockade. They also survive in normal numbers when their own signaling is blocked and many their synaptic partners die. While previous studies have demonstrated that the survival of newly migrated granule cells (GCs) is sensitive to activity levels, we demonstrate that all granule cells, regardless of their birthdate, depend on activity for their long-term survival. To show that the death and morphological defects that we observe in GCs are not due to cooperative effects of apoptotic signaling, but rather to a cell-autonomous requirement for MT cell excitatory input, we recapitulated a blockade of synaptic excitation in sparse GCs. Both knockdown of NMDAR-mediated excitation and chronic hyperpolarization led to similar morphological phenotypes as those we observe under MT cell signaling blockade. Finally, in some sensory systems that maintain spatial mappings from the periphery into higher processing areas, activity sculpts axonal branching and synapse formation or maintenance. MT cell projections do not maintain the OB's spatial map, but instead branch diffusely within cortical target regions. Using single MT cell axonal tracing, we show that neither OSN nor MT cell signaling is required for the gross branching patterns of MT cells or formation of appropriate numbers of presynaptic structures. This may reflect a mechanism for maintaining perceptual stability in the absence of stereotyped spatial maps