Compensatory Cerebellar Reorganization Following Spinal Cord Injury

Cerebellar function is critical for coordinating movement and motor learning. However, events that occur in the cerebellum following spinal cord injury (SCI) following the loss of spinocerebellar input have not been investigated in detail. We provide compelling preliminary evidence of cerebellar reorganization following SCI in adult rats. This is characterized by a loss of granule cell parallel fiber input to distal regions of the Purkinje cell dendritic tree and an increase in synaptic contacts to Purkinje cell presumably from climbing fibers originating in the contralateral inferior olive. This transynaptic reorganizational pattern is consistent with what is observed during development and in several transgenic models. However, this reorganizational pattern has never been described in response to SCI in adult rats and the functional significance is unknown at this time. The studies described in this proposal will extend these novel observations by accomplishing the following Aims: 1) Test the hypothesis that cerebellar reorganization in Purkinje cells follows a time course consistent with SCI induced loss of spinocerebellar inputs and that this reorganization pattern is maintained for chronic periods (up to 10 weeks following SCI), and 2) test the hypothesis that cerebellar reorganization is dependent, in part, on the loss of Cbln1, a synaptic organizing molecule that is critical for maintaining parallel fiber-Purkinje cell dendrite synaptic integrity. The studies proposed in this application will provide the first evidence of transynaptic reorganization in the cerebellum following SCI and provide support to investigate the functional significance of this understudied neuroplastic event.