Integration of Synaptic Excitation and Inhibition in the Cerebellar NucleiPublic Deposited
Large projection neurons of the cerebellar nuclei (CbN cells), whose activity generates movement, are inhibited by Purkinje cells and excited by mossy fibers. The high convergence, firing rates, and strength of Purkinje inputs predict powerful suppression of CbN cell spiking, raising the question of what activity patterns favor excitation over inhibition. Recording from CbN cells at near-physiological temperatures in cerebellar slices from weanling mice, we measured the amplitude, kinetics, voltage-dependence, and short-term plasticity of mossy fiber-mediated EPSCs. Unitary EPSCs were small and brief (AMPAR, ~1 nS, ~1 ms; NMDAR ~0.6 nS, ~7 ms) and depressed moderately. Using these experimentally measured parameters, we applied combinations of excitation and inhibition to CbN cells with dynamic clamp. Because Purkinje cells can fire coincident simple spikes during cerebellar behaviors, we varied the proportion (0-20 of 40) and precision (0-4 ms jitter) of synchrony of inhibitory inputs, along with the rates (0-100 spikes/s) and number (0-800) of excitatory inputs. Even with inhibition constant, when inhibitory synchrony was higher, excitation increased CbN cell firing rates more effectively. Partial inhibitory synchrony also dictated CbN cell spike timing, even with physiological rates of excitation. These effects were present with ≥10 inhibitory inputs active within 2-4 ms of each other. Conversely, spiking was most effectively suppressed when inhibition was maximally asynchronous. Thus, the rate and relative timing of Purkinje-mediated inhibition set the rate and timing of cerebellar output. The results suggest that increased coherence of Purkinje cell activity can facilitate mossy-fiber-driven spiking by CbN cells, in turn driving movements.
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