GABA and synaptic transmission in the cerebellum

Abstract

Several types of GABAergic neurons work in both the cortex and the nuclei of the cerebellum. Among them, Purkinje cells are the sole output neurons of the cortex. Basket and stellate cells in the molecular layer inhibit Purkinje cells and seem to contribute to the lateral inhibition of glutamatergic inputs of parallel fibers (axon of granule cells). Golgi cells in the granular layer constitute an inhibitory feedback loop by receiving parallel fiber inputs and suppressing the granule cell activity. The outputs of all the neuronal computation in the cortex are sent to the deep cerebellar nuclei through the axons of Purkinje cells. Some GABAergic neurons in the cerebellar nuclei innervate neurons in the inferior olive nuclei and regulate the synchrony of neuronal activities. Different types of GABA receptors are localized in their respective neurons in the cerebellum and seem to play specific roles at each type of synapses. The inputs and outputs of GABAergic neurons are regulated by the neuronal activities. Long-term potentiation (LTP) and long-term depression (LTD) at glutamatergic synapses on Purkinje cells have been reported. GABAergic synapses on Purkinje cells also show short-term and long-term synaptic plasticity such as depolarization-induced suppression of inhibition (DSI), depolarization-induced potentiation of inhibition (DPI), and rebound potentiation (RP). The former two are relatively short-term presynaptic regulation, and RP is a long-lasting postsynaptic regulation. Elaborate molecular regulation mechanism of RP has been studied. GABAergic synaptic plasticity and glutamatergic synaptic plasticity, depending on GABAergic synaptic inputs, have also been reported in the cerebellar nuclei. Several types of mutant mice lines affected in GABAergic neurons or GABAergic synaptic transmission have been reported. Mutant mice lacking Purkinje or Golgi cells and those with reduced GABAergic synaptic transmission to Purkinje cells have been studied. Auto-antibodies against GABA-related molecules have been found in some cerebellar ataxic patients, and the GABA mimetic drug seems to be effective in improving motor coordination in some ataxic patients.