[Seminar] "GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles" by Prof.Ryuichi Shigemoto

Speaker:
Prof.Ryuichi Shigemoto (Institute of Science and Technology Austria)
https://ist.ac.at/en/research/shigemoto-group/

Title:
GABA_B receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles

Abstract:
The enhancement of neurotransmission from medial habenula terminals by GABA_B receptor activation is the strongest known potentiation of transmitter release in the central nervous system but the underlying mechanisms remain enigmatic. We discovered that this potentiation is associated with a transition from facilitating tonic to depressing phasic mode of release caused by GABA_B receptor. This transition is activity-dependent and accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by genetic deletion of synaptoporin (SPO) and Ca²⁺-dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP in phasic release. A newly developed “Flash and Freeze-fracture” method revealed the release of SPO-associated vesicles in both tonic and phasic modes, whereas GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase in the phasic mode. Thus, we provide insights into the mechanisms underlying a new form of presynaptic modulation at a central synapse.

Contact: Dr.Kohgaku Eguchi, Uusisaari Unit (kohgaku.eguchi@oist.jp)