Coordination of spike timing among the neurons of the cerebellum

We tend to think of neurons as either excitatory or inhibitory, but certain neurons chemically inhibit their downstream targets while electrically exciting their neighbors. For example, in the cerebellum, molecular layer interneurons (MLIs) inhibit Purkinje cells (P-cells) via release of GABA but promote spiking in each other via gap junctions. What is gained by having an inhibitory neuron excite its neighbor? Here, we recorded activities of P-cells and MLIs as marmosets performed saccadic eye movements and found that spike timing in pairs of neighboring neurons of the same type exhibited a mathematical regularity: as firing rates increased, rate of spikes that were within 1ms of each other grew disproportionately while 2-4ms intervals were suppressed. To uncover the purpose of this coordination, during saccades we recorded thousands of neuron triplets in which two MLIs converged onto a single target P-cell. When the MLIs 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. However, when the MLIs spiked 2-4ms apart, the two spikes interfered with each other, producing partial cancellation. Thus, electrical coupling between inhibitory neurons orchestrated their spike timing so that as firing rates increased, the temporal intervals that induced downstream superposition were promoted while the intervals that caused interference were suppressed. Main findingsO_LISpike timing among neighboring P-cells and MLIs exhibited a mathematical pattern. C_LIO_LIAs firing rates increased, the rate of 1ms spike intervals grew disproportionately while 2-4ms intervals remained at or below chance. C_LIO_LIThe 1ms intervals between pairs of MLIs produced superposition on the downstream P-cell, whereas 2-4ms intervals produced interference. C_LIO_LIIndividual P-cell spike timing exhibited reliance on an internal clock. When a P-cell generated a spike, ephaptic coupling reset the internal clock of its neighboring P-cell. C_LIO_LIThis made the two clocks run on a common time base, regulating timing of spike production among the pairs. C_LIO_LIElectrical coupling among neighboring inhibitory neurons produced constructive superposition of their individual inhibitions on their downstream neurons while simultaneously reducing spiking events that resulted in counterproductive competition. C_LI