Nanodomain Coupling at an Excitatory Cortical Synapse

The coupling distance between presynaptic Ca2+ Influx and the sensor for vesicular transmitter release determines speed and reliability of synaptic transmission [1, 2]. Nanodomain coupling (<100 nm) favors fidelity [1, 2] and is employed by synapses specialized for escape reflexes [3] and by inhibitory synapses involved in synchronizing fast network oscillations [1]. Cortical glutamatergic synapses seem to forgo the benefits of tight coupling [4-6], yet quantitative detail is lacking [2, 7]. 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 [8] and well suited for analysis because they typically harbor only a single active zone [9]. 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.