MOLECULAR IDENTITY OF IDLE-ABLE TRANSMISSION SITES

Glutamatergic synapses contain two distinct transmission sites. The silenceable (SA) site, which is either silent, lacking AMPA type glutamate receptors, or unsilenced by containing AMPA type glutamate receptors. It mediates evoked transmission and is strengthened through Hebbian plasticity during development. The idle-able site (IA) is either ‘idled’ with unresponsive AMPA type glutamate receptors or ‘unidled’ with responsive AMPA type glutamate receptors. It mediates the homeostasis of miniature synaptic transmission and controls its frequency to be constant during development when silent synapses are unsilenced through experience-dependent plasticity. It remains unknown how these two transmission sites relate to previously described transmission modes through presumably different synaptic vesicle pools. Non-canonical SNARE proteins VAMP4 and VAMP7, known to contribute to asynchronous or spontaneous vesicles release, respectively, were found to be necessary for transmission from idled transmission sites. Further, we found additional evidence for a two-site binding of desensitization blockers to either block AMPA receptor desensitization or relief them from the idled state. Moreover, AMPA type glutamate receptors in the IA site are likely to have an ‘idling’ site that is distinct to the desensitization site. Altogether, we further describe the molecular identity of idle-able transmission sites with its contribution to regulate synaptic homeostasis.