Coordination of spike timing among the neurons of the cerebellum

Abstract

We tend to think of neurons as either excitatory or inhibitory, but certain neurons chemically inhibit their downstream targets while electrically exciting each other. For example, in the cerebellum, molecular layer interneurons type 1 (MLI1s) inhibit Purkinje cells (P-cells) via release of GABA but promote spiking in each other via gap junctions. P-cells inhibit nucleus neurons while exciting each other via ephaptic coupling. What is gained by excitatory interactions among inhibitory neurons? We recorded from the marmoset cerebellum during saccadic eye movements and found that spike timing in electrically coupled P-cell pairs, as well as MLI1 pairs, exhibited a mathematical regularity: as firing rates increased, the rate of spikes that were within 1ms of each other grew disproportionately while 2-4ms intervals were suppressed. We isolated triplets in which two MLI1s converged onto a single P-cell and found that if the MLI1s spiked within 1ms of each other, they produced superposition of their individual effects on their target; a deep inhibition followed by a post-inhibitory rebound. This enhanced the temporal precision in the downstream P-cells next spike. However, when the MLI1s spiked 2-4ms apart, the two spikes interfered with each other, producing partial cancellation. Thus, electrical coupling of inhibitory neurons promoted production of spike intervals that induced constructive superposition. This reduced the variance of spike timing in the downstream neuron.