Cellular-resolution mapping uncovers spatial adaptive filtering at the cerebellum input stage

Abstract

Long-term synaptic plasticity, in the form of either potentiation or depression (LTP or LTD), is thought to provide the substrate for adaptive computations in brain circuits. Although molecular and cellular processes of plasticity have been clarified to a considerable extent at individual synapses, very little is known about the spatiotemporal organization of LTP and LTD in local microcircuits. Here, we have combined multi-spot two-photon laser microscopy and realistic modeling to map the distribution of plasticity in multi-neuronal units of the cerebellar granular layer activated by stimulating an afferent mossy fiber bundle. The units, composed by ~300 active neurons connected to ~50 glomeruli, showed potentiation concentrated in the core and depression in the periphery. This plasticity was effectively accounted for by an NMDA receptor and calcium-dependent induction rule and was regulated by local microcircuit mechanisms in the inhibitory Golgi cell loops. The organization of LTP and LTD created effective spatial filters tuning the time-delay and gain of spike retransmission at the cerebellum input stage and provided a plausible basis for the spatiotemporal recoding of input spike patterns anticipated by the motor learning theory.