On the nature of GABAB receptors and their plasticity in the mammalian brain

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter of the mammalian CNS, essential for circuit function and behaviour. In the brain, GABA activates GABA A and GABA B receptors to modulate circuit activity on behaviourally relevant timescales. GABA B receptor signalling in pre- and postsynaptic domains of neurons is often overlooked, despite the strong inhibition it produces. Importantly, GABA B receptors are diversely phosphorylated and interact with various auxiliary subunits to modify function. This review compares the evidence for the expression and modulation of GABA B receptors, their effectors, and regulatory mechanisms between cell types, brain areas, and mammalian species, particularly focusing on the plasticity of these mechanisms and their relationship to neurological diseases such as epilepsy and dementia.