Septohippocampal transmission from parvalbumin-positive neurons features rapid recovery from synaptic depression

Feng Yi,Tavita Garrett,Heikki Haario,Karl Deisseroth,Emily Stone,J Josh Lawrence

doi:10.1038/s41598-020-80245-w

Abstract

Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca (hbox {PV}_{text{MS-DBB}}) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate hbox {PV}_{text{MS-DBB}} neuronal properties. hbox {PV}_{text{MS-DBB}} neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1–2 ms) 470 nm light pulses. To investigate hbox {PV}_{text{MS-DBB}} transmission, light pulses at 5–50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV (hbox {PV}_{text{HC}}) neurons generated trains of hbox {PV}_{text{HC}}-mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to hbox {PV}_{text{HC}} synapses, hbox {PV}_{text{MS-DBB}} synapses possessed lower initial release probability, transiently resisted STD at gamma (20–50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the hbox {PV}_{text{HC}} model, the hbox {PV}_{text{MS-DBB}} model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of hbox {PV}_{text{MS-DBB}} synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.

Highlights

Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca (P VMS-DBB ) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels
As expected from reported anti-PV labeling in rat[18,19,45,46,47] and viral expression in PV-CRE mice[48], PVMS-DBB neurons were localized near the MS midline and were generally absent from the lateral septal nucleus (LSN; Fig. S1A)
PVMS-DBB neurons exhibited a fast spiking phenotype that was distinct from SOMMS-DBB and ChATMS-DBB cells

Summary

Introduction

Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca (P VMS-DBB ) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. Optogenetic activation of local hippocampal PV (P VHC ) neurons generated trains of PVHC-mediated IPSCs in CA1 pyramidal neurons Both synapse types exhibited short-term depression (STD) of IPSCs. relative to PVHC synapses, PVMS-DBB synapses possessed lower initial release probability, transiently resisted STD at gamma (20–50 Hz) frequencies, and recovered more rapidly from synaptic depression. Previous studies have used a minimal extracellular stimulation technique to stimulate septohippocampal GABAergic axons onto hippocampal oriens-lacunosum moleculare (O-LM) interneurons and found reduced paired-pulse depression (PPD) and increased coefficient of variation (CV) relative to GABAergic input from local VIP interneurons[25,26] These observations suggest synaptic differences in short-term plasticity between septohippocampal and local GABAergic synapses. What is missing is a precise understanding of the synaptic dynamics of PVMS-DBB-mediated transmission onto specific interneuron targets This knowledge is needed to mechanistically link the activation of neurochemically-specific MS-DBB neuron subtypes to the generation of hippocampal theta and gamma rhythms. We conclude that resistance to STD is a key feature of PVMS-DBB-mediated transmission, facilitating robust information transfer from MS-DBB to hippocampus

Methods

Results

Conclusion