Synaptic shunting by a baseline of synaptic conductances modulates responses to inhibitory input volleys in cerebellar Purkinje cells

When processing synaptic input in vivo, large neurons in the brain must cope with thousands of events each second. Much work has focused on the specific processing of synchronous excitatory input volleys, both in cerebellar and cerebral cortical research. Here we pursue the question of how a continuous background of ongoing ‘noise’ inputs interacts with the processing of synchronous inhibitory input volleys. Specifically we examine the processing of inhibitory input transients in cerebellar Purkinje cells, which by inducing pauses in Purkinje cell spike activity may lead to a disinhibition of the deep cerebellar nuclei and thus to cerebellar motor command signals. We use the technique of dynamic clamping in vitro to simulate controlled patterns of in vivo like background inputs. We use electrical stimulation of inhibitory interneurons in the deep or upper molecular layer to create inhibitory input transients that lead to spike pauses in Purkinje cell activity. These pauses were much longer in the absence than in the presence of background inputs applied with dynamic clamping. We found that a significant amount of the synaptic current elicited by electrical stimulation was shunted by the background inputs. The overall amount of background conductance as well as the pattern of background inputs modulated spike pause duration in a specific manner. This modulation by shunting may be employed in vivo to evaluate the salience of specific sensory input received by cerebellar cortex.