Nanodomain Coupling at an Excitatory Cortical Synapse
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Summary

The coupling distance between presynaptic Ca2+ influx and the sensor for vesicular transmitter release determines speed and reliability of synaptic transmission []. Nanodomain coupling (<100?nm) favors fidelity [] and is employed by synapses specialized for escape reflexes [] and by inhibitory synapses involved in synchronizing fast network oscillations []. Cortical glutamatergic synapses seem to forgo the benefits of tight coupling [], yet quantitative detail is lacking []. The reduced transmission fidelity of loose coupling, however, raises the question whether it is indeed a general characteristic of cortical synapses. Here we analyzed excitatory parallel fiber to Purkinje cell synapses, major processing sites for sensory information [] and well suited for analysis because they typically harbor only a single active zone []. We quantified the coupling distance by combining multiprobability fluctuation analyses, presynaptic Ca2+ imaging, and reaction-diffusion simulations in wild-type and calretinin-deficient mice. We found a coupling distance of <30?nm at these synapses, much shorter than at any other glutamatergic cortical synapse investigated to date. Our results suggest that nanodomain coupling is a general characteristic of conventional cortical synapses involved in high-frequency transmission, allowing for dense gray matter packing and cost-effective neurotransmission.

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