The broad goal of the research is to better understand cerebellar function by investigating the neuronal signal processing underlying compensatory eye movements. For the most part the experimental method will be manipulation of the extracellularly recorded activity of cortical interneurons and Purkinje cells in the cerebellar flocculus through presentation of natural visual and vestibular stimuli to the rabbit. A central tenet is that to understand how the cerebellum functions as a 'neuronal machine', it is necessary to know, from a systems point of view, the signal content and signal processing of cerebellar cortical interneurons (granule-, Golgi-, basket/stellate-, and unipolar brush cells). Presently, this knowledge is hardly available, particularly for an awake, behaving animal. Consequently, one focus is investigation of the signal content and processing of floccular interneurons in the awake rabbit presented with natural stimuli. The various types of cerebellar cortical interneurons can now be identified using our recent finding the each type of cerebellar cortical interneuron has a characteristic pattern of spontaneous activity. A second focus is the signal content and synchrony of climbing fiber activity, recorded as floccular Purkinje cell complex spikes.
In Specific Aim 1 the relations between the vestibularly and visually induced modulation of floccular interneuronal activity and aspects of eye movement behavior (kinematics, vestibulo-ocular response gain, and vergence) will be investigated in the rabbit.
Specific Aim 2 will use local cortical injections of the GABA-A receptor blocker gabazine to examine the role of Golgi cell inhibition in producing the high frequency burst activity characteristic of rabbit floccular granule cells.
In Specific Aim 3 the signal content of the mossy fiber input to the rabbit flocculus arising from the brainstem vestibular and prepositus hypoglossi nuclei will be determined so as to help assess what signal transformations occur at mossy fiber-granule cell synapses.
In Specific Aim 4 the contribution of the prepositus hypoglossi nuclei to the vestibularly induced floccular complex spike modulation will be studied using ablative and chemical lesions.
Specific Aim 5 deals with .the role of complex spike synchrony in motor behavior. Synchrony during vestibular stimulation will be compared to that occurring without stimulation to evaluate the hypothesis that synchrony will be altered during vestibular stimulation because of the modulation of the GABA input from the prepositus hypoglossi nuclei to the dorsal cap of the inferior olive. Understanding the signal processing of cerebellar cortical interneurons and climbing fiber messages is relevant to comprehending the cerebellum's role both in the moment-to-moment control of movement and posture and in learning adaptive motor behaviors. Cerebellar dysfunctions are often due to genetic dysfunctions, and knowledge of signal processing in the rabbit cerebellum has already been shown to be transferable to mouse models of gene-based dysfunctions. . ?;-
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