Four specific projects aimed at increasing our understanding of how olivo-cerebellar circuits are altered by repeated stimulation are proposed:. 1. Climbing fiber-evoked conjunctive depression of parallel fiber synapses on nodular Purkinje cells during natural vestibular stimulation. The modification of simple spike discharge (SSs) by climbing fiber responses (CFRs) might be caused, in part, """"""""long term depression"""""""" (LTD) characterized in vitro. We will examine the influence of vestibularly-evoked CFRs on the amplitude of a parallel fiber volley evoked in the same cerebellar folium. This will test directly the idea that the CF depolarization depresses the conjunctively-evoked parallel fiber input to the Purkinje cell. This idea could explain temporal features of cerebellum plasticity. 2. Changes in mRNA isolated from the optokinetic olivocerebellar pathway as a consequence of prolonged optokinetic stimulation. Prolonged horizontal optokinetic stimulation activates neurons in an optokinetic circuit that includes the retina, nucleus of the optic tract, dorsal cap, flocculus and nodulus. We will use the technique of """"""""differential display"""""""" to discover likely molecular candidates for modification during prolonged optokinetic stimulation. Total RNA from """"""""optokinetically stimulated"""""""" and """"""""control tissue"""""""" will be isolated, amplified, cloned, sequenced and compared to existing data bases. This research will establish candidate molecular substrates for cellular plasticity. 3. Electrophysiological analysis of """"""""Pre- olivary vestibular"""""""" plasticity. We have identified a """"""""new"""""""" vestibular nucleus whose neurons provide the source of the vestibular input to the inferior olive. We will determine if this """"""""pre-olivary vestibular nucleus"""""""" is the source of entrainment of olivary neurons by periodic vestibular stimulation. This will help us understand how vestibular information contributes to olivo- cerebellar function. 4. Spatial topography of the uvula-nodulus studied with histochemical and electrophysiological methods. The topographic climbing fiber map of vestibular and optokinetic information onto the uvula-nodulus will be extended using anatomical techniques to trace distribution of the individual branches of the vestibular nerve onto this climbing fiber map. Using physiological techniques, the contribution of naturally modulated neck afferents onto the uvula-nodulus will also be studied. These experiments will enable us to understand how sensory-motor maps regulate and modify movement.
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