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

Noemi Holderith,Mohammad Aldahabi,Mohammad Aldahabi,Zoltan Nusser

doi:10.3389/fnsyn.2021.773209

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 the hippocampus of rodents, somatostatin and mGluR1α expressing interneurons (mGluR1α+ INs) receive small, facilitating excitatory postsynaptic currents (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 threefold larger amplitudes with less pronounced short-term facilitation, which might be the consequence of the loss of either 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 to mGluR1α+ IN connection. Our results demonstrate that Munc13-1 alone is capable of imposing low Pv at PC to mGluR1α+ IN synapses and Munc13-2 has yet an unknown role in this synapse.

Highlights

Postsynaptic target cell type-dependent differences in synaptic efficacy and short-term plasticity of excitatory synapses (Ali and Thomson, 1997, 1998; Reyes et al, 1998; Scanziani et al, 1998; Sun et al, 2005) have profound impacts on cortical network dynamics (Pouille and Scanziani, 2004)
We describe that: (1) bMunc13-2 is selectively enriched in active zones (AZs) of CA1 pyramidal cells (PCs) axon terminals that target mGluR1α+ INs. (2) Munc13-1 is present in Munc13-2 containing CA1 PC AZs, together with Rim1/2, Cav2.1, and Bassoon
(5) CA1 PC to mGluR1α+ /O-LM IN synapses lacking Munc13-2 display very similar functional properties compared to Munc13-2 containing control synapses

Summary

Introduction

Postsynaptic target cell type-dependent differences in synaptic efficacy and short-term plasticity of excitatory synapses (Ali and Thomson, 1997, 1998; Reyes et al, 1998; Scanziani et al, 1998; Sun et al, 2005) have profound impacts on cortical network dynamics (Pouille and Scanziani, 2004). Presynaptic neurotransmitter receptors could powerfully influence neurotransmitter release and short-term plasticity, in the presence of a large number of presynaptic receptor blockers synapses still show very diverse functional properties. This diversity is likely the consequence of the heterogeneous molecular components of the AZ matrix that mediate synaptic vesicles (SVs) docking, priming, and release (Sudhof, 2012). In 90% of the axon terminals of cultured PCs, Munc primed vesicles have high Pv and the synapses display short-term depression while in 10% of boutons, the presence of Munc, in the absence of Munc, confers low Pv and short-term facilitation (Rosenmund et al, 2002). Munc immunolabeling in the hippocampus showed an uneven distribution of the protein with strong staining in the stratum oriens of the CA1 area (Kawabe et al, 2017) where most of the dendrites of mGluR1α+ INs are located, raising the question whether the low Pv of CA1 PC to mGluR1α+ IN synapses could be the consequence of the presence of Munc as a priming factor?

Methods

Results

Conclusion