Subcellular vesicular aggregations of GABAB R1a and R1b receptors increase with age in neurons of the developing...

GABA(B) receptors play a critical neuromodulatory role in the central nervous system. It has been suggested that both the functional role and the cellular distribution of GABA(B) receptors in the neuronal network change during post-natal maturation. In the present study, the cellular and subcellular distribution patterns of the GABA(B) R1a/b receptors have been analysed in different brain regions of the mouse using immunocytochemistry with isoform-specific antisera. GABA(B) R1-immunoreactivity (IR) was present from the first post-natal day (P0) on in most regions of the brain. Neurones exhibited diffuse GABA(B) R1-IR labelling throughout somata and larger proximal dendrites as well as some fine neuronal processes. After P5, distinct punctuated staining was apparent. The number of such GABA(B) IR granules per cell increased with age in a sigmoidal manner from P5 to P60. Electron microscopy revealed GABA(B) IR as clusters of small clear vesicles of 30-50 nm diameter within the cytoplasm and close to the cell membrane at extrasynaptic locations, as well as at pre-synaptic and post-synaptic specialisations. The increase in GABA(B) R1-IR punctuate staining during brain maturation points to increasing functional participation and heterogeneity of GABA(B) receptors as the complexity of the central nervous system expands with growth and development.