Visual and vestibular stimulation modulate the discharge of Purkinje neurons in the cerebellar uvula-nodulus and contribute to plastic changes in reflexive eye movements. We will relate these changes in Purkinje cell discharge to the micro circuitry of the cerebellum. We will also examine transcriptional changes in the cerebellum and dorsal cap of the inferior olive induced about prolonged optokinetic stimulation. The research will answer four questions: 1. What is the relative importance of vestibular climbing and mossy fiber pathways in modulating the simple spike (SS) discharge of Purkinje neurons? In rabbits with unilateral labyrinthectomies, mossy and climbing fibers pathways carrying vestibular information, project to opposite sides of the uvula-nodulus. One side receives only modulated vestibular climbing fiber signals (CFRs) and the other receives only vestibular mossy fiber signals. We will record Purkinje cell activity on both sides. We predict that vestibularly-nodulated CFRs are necessary and sufficient to account for the observed modulation of SSs. 2. Does the uvula-nodulus contribute to vestibular-optokinetic adaptation? We will measure the amplitude and time course of adaptation of eye movements evoked by conflicting vestibular and optokinetic stimulation in normal and uvula-nodulus-lesioned rabbits. We predict that the gain of the vertical vestibuloocular reflex will recover immediately after such conflict in both normal and lesioned rabbits. However, the time course of recovery of the gain of the vertical optokinetic reflex will be lengthened in lesioned rabbits. 3. Does the release of corticotropin-releasing factor (CRF) by inferior olivary neurons protect Purkinje cells from excitotoxicity during climbing fiber-evoked activity? CRF is co-released by all climbing fibers along with excitatory amino acids. The release of CRF may protect Purkinje neurons against excitotoxicity. In transgenic CRF knockout mice, we predict that optokinetically-evoked climbing fiber activity, without CRF co-release, will cause degeneration and/or altered transcription in the flocculus. We will use """"""""differential display"""""""" and a gene array spotting system to compare changes in gene transcription induced by prolonged optokinetic stimulation in normal and CRF knockout mice. 4. Does optokinetically-evoked activity in dorsal cap neurons influence gene transcription? Optokinetic stimulation of dorsal cap neurons causes changes in gene transcription. Dorsal cap neurons are the only inferior olivary neurons that do not express calbindin. We will use """"""""differential display"""""""" to identify mRNAs in dorsal cap neurons whose proteins might be responsible for two functions: 1) Axonal transport of CRF , and 2) Calcium binding.
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