AUTHOR=Holderith Noemi , Aldahabi Mohammad , Nusser Zoltan 

TITLE=Selective Enrichment of Munc13-2 in Presynaptic Active Zones of Hippocampal Pyramidal Cells That Innervate mGluR1α Expressing Interneurons

JOURNAL=Frontiers in Synaptic Neuroscience

VOLUME=Volume 13 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/synaptic-neuroscience/articles/10.3389/fnsyn.2021.773209

DOI=10.3389/fnsyn.2021.773209

ISSN=1663-3563

ABSTRACT=Selective distribution of proteins in presynaptic active zones (AZs) is a prerequisite for generating postsynaptic target cell type-specific differences in presynaptic vesicle release probability (Pv) and short-term plasticity - a characteristic feature of cortical pyramidal cells (PCs). In rodent hippocampus, somatostatin and mGluR1α expressing interneurons (mGluR1α+ INs) receive small, facilitating EPSCs from PCs and express Elfn1 that trans-synaptically recruits mGluR7 into the presynaptic AZ of PC axons. Here we show that Elfn1 also has a role in the selective recruitment of Munc13-2, a synaptic vesicle priming and docking protein, to PC AZs that innervate mGluR1α+ INs. In Elfn1 knock-out mice, unitary EPSCs (uEPSCs) in mGluR1α+ INs have 3-fold larger amplitudes with less pronounced short-term facilitation, which might be the consequence of the loss of mGluR7 or Munc13-2 or both. Conditional genetic deletion of Munc13-2 from CA1 PCs results in the loss of Munc13-2, but not mGluR7 from the AZs and has no effect on the amplitude of uEPSCs and leaves the characteristic short-term facilitation intact at PC – mGluR1α+ IN connection. Our results demonstrate that Munc13-1 alone is capable of imposing low Pv at PC – mGluR1α+ IN synapses and Munc13-2 has yet an unknown role in this synapse.