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

Abstract

Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca (PVMS-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 PVMS-DBB neuronal properties. PVMS-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 PVMS-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 (PVHC) neurons generated trains of PVHC-mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, 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. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the PVHC model, the PVMS-DBB model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of PVMS-DBB synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus. 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 ( PV HC ) neurons generated trains of PV HC-mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to PV HC synapses, PV 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 PV HC model, the PV MS-DBB model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of PV MS-DBB synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.