A key factor determining the fidelity of chemical neurotransmission is the coupling distance between the site of Ca²⁺ influx and the Ca²⁺ sensor for vesicular transmitter release. Tight, nanodomain coupling (<100nm) is favoring efficacy, reliability and speed of transmission[1]. Contrary to other synapses, excitatory cortical synapses seem to work at loose, microdomain coupling and forgo these advantages[2]. Yet, most of the investigations were performed on very young mice, while recently the adult cerebellar parallel-fiber (PF) synapse, probably the most abundant excitatory cortical synapses in the brain, was found to operate at nanodomain coupling[3]. Interestingly, the giant Calyx of Held synapse in the brain stem seems to undergo an ontogenetic shift from loose to tight coupling2. Here, we aim at characterizing developmental changes in the coupling distance of PF synapses, using bath application of different concentrations of AM esters of exogenous Ca²⁺ chelators for interference with synaptic transmission[4] in young and adult mice. Our experiments on adult PF synapses show that only the fast chelator BAPTA interfered with transmission, while the slower EGTA had no effect. This is in accord with the previous finding of nanodomain coupling in adult PF terminals³ and validates AM-chelator application as a tool for estimating coupling at PF synapses. Prospective experiments will reveal whether tight coupling is a characteristic of the PF synapse or whether a developmental shift from loose to tight coupling takes place as in the Calyx.

[1]Buccurenciu et al., Neuron, 2008

[2]Eggermann et al., Nat Rev Neurosci, 2012

[3]Schmidt et al., Curr Biol, 2013 im Druck

[4]Adler et al, J Neurosci, 1991