ACTIVATION OF CEREBELLAR INHIBITORY LOOPS: EVIDENCE FOR NOVEL GRANULE CELL-GOLGI CELL CONTACTS IN THE GRANULAR LAYER

The granular layer, the input stage of the cerebellar cortex, is an important target of EtOH that is populated by two main neuronal types, excitatory GrCs and inhibitory Golgi cells (GoCs). The function of these neurons is altered by acute EtOH exposure. Mossy fibers (mfs) provide excitatory inputs to both neuron types; GoCs are also excited by GrCs, and their output inhibits GrCs. Thus mfs activate local feed-forward and feed-back inhibitory loops. Sensory input can either activate a GoC with high temporal precision, or evoke less precisely timed responses. While direct input from mfs may trigger GoC firing with millisecond precision, the functional impact of GrC input on GoC firing is unknown. GrC-GoC contacts are believed to occur in the molecular layer, between parallel fibers (pfs) and GoC apical dendrites, although morphological data also propose the presence of contacts between the GrC ascending axon (aa) and GoC basolateral (bl) and apical dendrites. Using a combination of electrophysiological, 2-photon Ca2+-imaging and EM approaches, we have obtained evidence for functional aa-GoC contacts occurring in the rat GL onto bl dendrites. EPSCs from these contacts (aaEPSCs) have fast kinetics, similar to mf-evoked EPSCs (mf-EPSCs), in contrast with the slow kinetics of pf-evoked EPSCs. mf spikes evoke both mono-synaptic mf- and di-synaptic aa-EPSCs, which may summate to evoke a GoC spike within milliseconds. Hence, the impact of novel aaEPSCs on GoC firing may parallel the one of mf inputs, contributing to generate fast GoC responses, which may allow for precise control of the time window for information flow through GrCs. The pf–GoC input is more complex, involving weak excitatory and inhibitory metabotropic components, and this may implement spatial contrast enhancement upon intense pf excitation. The potential impact of EtOH on aa and pf GoC inputs will be discussed.