Activity-dependent development of inhibitory synapses and innervation pattern: role of GABA signalling and beyond

GABA-mediated synaptic inhibition is crucial in neural circuit operations. The development of GABAergic inhibitory synapses and innervation pattern in mammalian neocortex is a prolonged process, extending well into the postnatal period, and is regulated by neural activity and experience. Accumulating evidence supports the hypothesis that GABA signalling acts beyond synaptic transmission and regulates inhibitory synapse development; in other words, similar to glutamate signalling at developing excitatory synapses, GABA may coordinate pre- and post-synaptic maturation at inhibitory synapses. These findings raise numerous questions regarding the underlying mechanisms, including the role of GABA receptors and their link to synaptic adhesion molecules. Since synapse formation is a crucial component of axon growth, GABA signalling may also shape the axon arbor and innervation pattern of inhibitory neurons. A mechanism unique to GABAergic neurons is activity-dependent GABA synthesis, largely mediated through activity-regulated transcription of the rate-limiting enzyme GAD67. Such cell-wide as well as synaptic regulation of GABA signalling may constitute a mechanism by which input levels and patterns onto GABAergic neurons shape their innervation pattern during circuit development.