UC San Diego

Surface diffusion of postsynaptic receptors shapes synaptic transmission. Presynaptic receptors also influence transmission, but the relevance of their mobility for synaptic function is unknown. Using single-particle tracking with quantum dots, we show that calcium-permeable α7-containing nicotinic acetylcholine receptors (α7-nAChRs), capable of promoting transmitter release, are mobile on presynaptic terminals but constrained in synaptic space on rat hippocampal neurons in culture. Additional immobilization of presynaptic α7-nAChRs by antibody crosslinking increases glutamate release capacity as seen in the frequency of spontaneous miniature postsynaptic currents and the size of the readily releasable pool of transmitter. Conversely, blocking glutamate release by targeting tetanus toxin to individual synapses increases α7-nAChR dwell time at presynaptic sites. The effects on release require functional α7-nAChRs and may to depend on CAST/ELKS (calpastatin/glutamine, leucine, lysine, and serine-rich protein), which an unbiased proteomic screen yielded. The results support a new homeostatic regulatory mechanism in which α7-nAChR restrain may be adjusted as needed at presynaptic sites via active zone proteins to maintain transmitter release capability.