The long term goal of this work is two-fold: to understand how the integrity of synapses is normally maintained and to understand the compensatory mechanisms involved in adaption of the nervous system to aging-induced changes in synaptic stability. Recent experiments have implicated Schwann cells (SCs) as important players in synaptic plasticity during development and regeneration, and experiments are proposed here to investigate the role of terminal SCs in aging-induced plasticity of synaptic connections.
In Aim #1, the dynamic interaction between SCs and nerves will be examined by vital staining and repeated in vivo imaging in normal adult and old animals. It will thus be possible to determine whether the morphological instability of aged junctions, characterized in the pas as an increase in axon outgrowths and regressions, is the result of dynamic changes in SCs and their processes.
Aim #2 will use cell ablation techniques and in vivo imaging to ask whether SCs are necessary to maintain normal synaptic integrity and address the consequences of SC ablation for the disruption of synaptic integrity that occurs with age.
Aim #3 will address whether the changes in synaptic integrity observed at aging junctions are a consequence of changes in SC responsiveness to neuregulins. Collectively, these studies will provide a better understanding of the mechanisms behind increased synaptic plasticity observed with aging.
