Unusually slow spike frequency adaptation in deep cerebellar nuclei neurons preserves linear transformations on the sub-second time scale

Abstract

AbstractPurkinje cells (PCs) are spontaneously active neurons of the cerebellar cortex that inhibit glutamatergic projection neurons within the deep cerebellar nuclei (DCN) that in turn provide the primary cerebellar output. Brief reductions in PC firing rapidly increase DCN neuron firing. However, prolonged reductions in PC inhibition, as seen in some disease states, certain types of transgenic mice, and in acute slices of the cerebellum, do not evoke large sustained increases in DCN firing. Here we test whether there is a mechanism of spike-frequency adaptation in DCN neurons that could account for these properties. We find that prolonged optogenetic suppression of PC synapses in vivo transiently elevates PC firing that strongly adapts within ten seconds. We perform current-clamp recordings at near physiological temperature in acute brain slices to examine how DCN neurons respond to prolonged depolarizations. Adaptation in DCN neurons is exceptionally slow and bidirectional. A depolarizing current step evokes large initial increases in firing that decay to less than 20% of the initial increase within approximately ten seconds. Such slow adaptation could allow DCN neurons to adapt to prolonged changes in PC firing while maintaining their linear firing frequency-current relationship on subsecond time scales.