Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse.

The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission. • Reciprocal changes in release probability and release site number during development • Maintained reliance on P/Q-type Ca2+ channels, but reduced sensitivity to Ca2+ chelators • Ca2+ channel clusters throughout development, docked vesicle clusters at later stages • Developmental transformation from more random to more clustered coupling nanotopographies Chen et al. combine paired recordings, structural analysis, and modeling to examine the coupling between presynaptic Ca2+ channels and release sensors in an inhibitory GABAergic synapse at different developmental time points. The results reveal a developmental transformation from more random organization to precise point-to-point synaptic transmission at the nanometer scale. [ABSTRACT FROM AUTHOR]