This proposal aims to determine the functional significance of inhibition in cerebellar cortex. It is predicted from previous experiments and computer simulations that normal cerebellar function depends on a constant action of inhibitory input to Purkinje cells, which provide the only output from cerebellar cortex. The hypothesis that the computational algorithm taking place in cerebellum critically depends on the precise temporal and spatial pattern of this inhibition will be tested. A combined physiological and computer modeling approach will be used. In vitro whole cell recordings will be obtained to determine the time course and amplitude of single inhibitory inputs to Purkinje cells, and the relative contribution of inhibition to the soma and the dendrite. Realistic synaptic conductance patterns resulting from the input of many synapses will be generated with a computer model and will be applied to Purkinje cells in vitro with the dynamic current clamp technique. This manipulation is suitable to determine the accurate input-output function of Purkinje cells with respect to inhibition. Comparison of modeling and physiological results with the same input patterns will guide the predictions and analysis of the computation taking place in Purkinje cells. In vivo intracellular recordings in anesthetized rats will be used to determine the spatial pattern of inhibition of Purkinje cells with peripheral tactile stimuli that activate known receptive fields in the input layer of cerebellar cortex. The ultimate goal of this work is to produce a realistic computer model of network computation in cerebellum. Such modeling is vital in understanding the non-linear dynamics in the cerebellar neural network. Existing theories and models of cerebellar cortical function largely disregard the involvement of inhibition, without data to support this bias. The proposed work will test this assumption and will likely suggest a critical role for inhibition in cerebellar computation. New insights into the computational algorithm taking place in cerebellum are necessary to guide the understanding of the mechanisms underlying cerebellar movement disorders.
| Suter, K J; Jaeger, D (2004) Reliable control of spike rate and spike timing by rapid input transients in cerebellar stellate cells. Neuroscience 124:305-17 |
| Gauck, Volker; Jaeger, Dieter (2003) The contribution of NMDA and AMPA conductances to the control of spiking in neurons of the deep cerebellar nuclei. J Neurosci 23:8109-18 |
| Jaeger, Dieter (2003) No parallel fiber volleys in the cerebellar cortex: evidence from cross-correlation analysis between Purkinje cells in a computer model and in recordings from anesthetized rats. J Comput Neurosci 14:311-27 |
| Gauck, V; Thomann, M; Jaeger, D et al. (2001) Spatial distribution of low- and high-voltage-activated calcium currents in neurons of the deep cerebellar nuclei. J Neurosci 21:RC158 |
