The goal of this project is to contribute to understanding the development of synaptic function in the central nervous system (CMS). I propose to focus on investigating the maturation of the climbing fiber-Purkinje cell synapse and to test the hypothesis that the TrkB receptor plays a role in regulating the switch from multiple to single climbing fiber innervation of Purkinje cells during postnatal development of the cerebellar cortex. To this end, I propose to investigate the time course and functional maturation of climbing fiber innervation of Purkinje cells, using as experimental model transgenic mice that harbor either a hypomorphic level of TrkB expression or a targeted deletion of TrkB in the cerebellum. To do this I propose studies that combine behavioral, neuroanatomical, molecular and electrophysiological approaches that will offer me extensive training in an intellectually rich environment. The results of my preliminary studies suggest that hypomorphic or TrkB-null mice are behaviorally ataxic and show a persistence of multiple climbing fiber innervation.
| Johnson, Erin M; Craig, Ethan T; Yeh, Hermes H (2007) TrkB is necessary for pruning at the climbing fibre-Purkinje cell synapse in the developing murine cerebellum. J Physiol 582:629-46 |
