The presynaptic scaffolding protein Piccolo organizes the readily releasable pool at the calyx of Held

Abstract

Synaptic vesicles (SVs) are released at the active zone (AZ), a specialized region of the presynaptic plasma membrane organized by a highly interconnected network of multi-domain proteins called cytomatrix of the active zone (CAZ). Two core components of the CAZ are the large, highly homologous scaffolding proteins Bassoon and Piccolo, whose function is not well understood. In order to investigate their role in synaptic transmission, we established the shRNA-mediated in vivo knock-down (KD) of Bassoon and Piccolo at the rat calyx of Held synapse. KD of Bassoon and Piccolo, separately or simultaneously, did not affect basic SV release. However, short-term depression (STD) was prominently increased by the KD of Bassoon while KD of Piccolo only had a minor effect. The observed alterations in STD were readily explained by reduced SV replenishment in synapses deficient in either of the proteins. Thus, the regulation of SV refilling during ongoing synaptic activity is a shared function of Bassoon and Piccolo, although Bassoon appears to be more efficient. Moreover, we observed the recruitment of slowly releasing SVs of the readily-releasable pool (RRP), which are normally not available for AP-induced release, during high frequency stimulation in Piccolo-deficient calyces. Therefore, our results suggest a novel and specific role for Piccolo in the organization of the subpools of the RRP.

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