Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex

Abstract

Circuitry of the cerebellar cortex is regionally and functionally specialized. Unipolar brush cells (UBCs), and Purkinje cell (PC) synapses made by axon collaterals in the granular layer, are both enriched in areas that control balance and eye-movement. Here we find a link between these specializations: PCs preferentially inhibit mGluR1-expressing UBCs that respond to mossy fiber inputs with long lasting increases in firing, but PCs do not inhibit mGluR1-lacking UBCs. PCs inhibit about 29% of mGluR1-expressing UBCs by activating GABAA receptors (GABAARs) and inhibit almost all mGluR1-expressing UBCs by activating GABABRs. PC to UBC synapses allow PC output to regulate the input layer of the cerebellar cortex in diverse ways. GABAAR-mediated feedback is fast, unreliable, noisy, and suited to linearizing input-output curves and decreasing gain. Slow GABABR-mediated inhibition allows elevated PC activity to sharpen the input-output transformation of UBCs, and allows dynamic inhibitory feedback of mGluR1-expressing UBCs.