Cerebellar Granule Cell

Abstract

The cerebellar granule cells are the most numerous neurons of the brain. They are also among those with the simplest structure by emitting just four short unbranched dendrites innervated by the mossy fibers and a thin axon that branches into the parallel fibers. The granule cells are the only excitatory neurons of the cerebellum (apart of the recently discovered unipolar brush cells (UBCs)) and receive inhibition uniquely through the Golgi cells. Since their early discovery by Camillo Golgi and Ramon y Cajal at the end of the nineteenth century, the granule cells have been the object of intensive investigation. The milestones have been the field recording of their activity in the 1960s, the discovery of their GABAergic inhibition in the 1970s and of their glutamatergic excitation in the 1980s, and the characterization of their membrane and synaptic mechanisms with patch-clamp techniques in the 1990s. Then in the last two decades, a series of careful electrophysiological and imaging investigations have unveiled major yet undisclosed functional properties of granule cells leading to a reevaluation of the function of the whole cerebellar cortex. The initial guess that granule cells simply retransmit incoming information (“integrate and fire” behavior) has been challenged by recent results showing that granule cells are endowed with nonlinear excitable properties. Moreover, the assumption that all granule cells operate in the same stereotyped way proved untrue, revealing diversification of functions. Finally, the prediction that the mossy fiber-granule cell synapse would lack long-term plasticity has been reversed by the discovery of complex forms of long-term potentiation and depression (LTP and LTD). These properties provide a new view of the granule neurons, which operate complex transformations of input signals in the spatiotemporal domain providing a substantial contribution to the computation and learning properties of the cerebellum.