Unconventional GABA release: mechanisms and function

GABA is the main inhibitory neurotransmitter in the mammalian brain, and perturbed GABA signalling is the underlying cause of many neurological and psychiatric disorders. Synaptic release of GABA and the functional consequences of its receptor activation have been studied extensively. However, GABA can also be released in unconventional ways. For example, GABA can provide a retrograde signal, released from parts of the neuron other than the axon terminal. Alternatively, GABA can be released from neurons or glial cells by the reversal of transporters, or by other non-vesicular release mechanisms. In this review, we provide an overview of the recent findings regarding the mechanisms and functions of unconventionally released GABA and discuss the physiological significance of such neural regulation.