GABA Pathways and Receptors

Abstract

GABAergic neurons including Purkinje cells play critical roles in cerebellar neuronal circuits. In the cerebellar cortex, molecular layer interneurons (stellate and basket cells) provide feedforward inhibitory loops between parallel fibers and Purkinje cells, and granular layer interneurons (Golgi cells) form feedback inhibition loops between granule cells. Some GABAergic neurons in the cerebellar nuclei inhibit inferior olive neurons, which send excitatory climbing fibers to the cerebellum. The cerebellar nuclear neurons and Purkinje cells are rare examples of GABAergic projection neurons. Cerebellar neurons express various types of ionotropic and metabotropic GABA receptors, which mediate the effects of GABA, and granule cells express extrasynaptic ionotropic GABA receptors that play a role in tonic inhibition. Both excitatory synapses on GABAergic neurons and GABAergic synapses show neuronal activity dependent plasticity, which contribute to motor learning. Several types of mutant mice defective in GABAergic neurons or synaptic functions have been found or generated, and they show failures in motor coordination and/or motor learning. Dysfunctions of cerebellar GABAergic system have been suggested to be causes of ataxia, and a GABA-mimetic drug improves motor coordination in some ataxic patients.