Subcellular regulation of metabotropic GABA receptors in the developing cerebellum

Our understanding of GABAergic and glutamatergic neurotransmission in the CNS has been greatly influenced with the discovery and subsequent investigations of the metabotropic gamma-aminobutyric acid (B) (GABA(B)) receptors. These G-protein coupled receptors mediate slow inhibitory neurotransmission and are widely expressed and distributed in the cerebellum, where they play critical roles in neuronal excitability and modulation of synaptic neurotransmission. Their function is modulated by interaction with effector ion channels, notably inwardly rectifying K(+) channels and voltage-gated Ca(2+) channels. The receptors are encoded by two distinct subunits, GABA(B1) and GABA(B2), both of which are required in order to function normally in vivo, as shown in recombinant expression systems and in GABA(B1) -/- mice. The GABA(B1) and GABA(B2) subunits exhibit overlapping distributions in the cerebellar cortex, both at pre- and postsynaptic sites, during development and adulthood. They are in particular abundant in Purkinje cells prior to synaptogenesis and throughout postnatal development. Using high-resolution immunohistochemical techniques at the electron microscopic level in combination with quantitative analysis and three-dimensional reconstructions, it has recently been demonstrated that GABA(B) receptors undergo changes in localization on the surface of Purkinje cell dendrites and spines during postnatal development in association with the establishment and maturation of excitatory synapses. Due to this dynamic regulation, the highest densities of GABA(B1) and GABA(B2) subunits occur around the glutamatergic synapses between Purkinje cell spines and parallel fibre varicosities. This review highlights recent studies that have shed further light on the subcellular localization during postnatal development and the cell surface dynamics of GABA(B) receptors.