Report Nanodomain Coupling at an Excitatory Cortical Synapse

influx andthe sensor for vesicular transmitter release determinesspeedandreliabilityofsynaptictransmission[1,2].Nanodo-main coupling (<100 nm) favors fidelity [1, 2] and isemployed by synapses specialized for escape reflexes [3]and by inhibitory synapses involved in synchronizing fastnetwork oscillations [1]. Cortical glutamatergic synapsesseem to forgo the benefits of tight coupling [4–6], yet quan-titative detail is lacking [2, 7]. The reduced transmissionfidelity of loose coupling, however, raises the questionwhether it is indeed a general characteristic of corticalsynapses. Here we analyzed excitatory parallel fiber to Pur-kinje cell synapses, major processing sites for sensoryinformation [8] and well suited for analysis because theytypically harbor only a single active zone [9]. We quantifiedthe coupling distance by combining multiprobability fluctu-ation analyses, presynaptic Ca