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 ($$\hbox {PV}_{\text{MS-DBB}}$$ PV 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 $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neuronal properties. $$\hbox {PV}_{\text{MS-DBB}}$$ PV 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 $$\hbox {PV}_{\text{MS-DBB}}$$ PV 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 ($$\hbox {PV}_{\text{HC}}$$ PV HC ) neurons generated trains of $$\hbox {PV}_{\text{HC}}$$ PV HC -mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to $$\hbox {PV}_{\text{HC}}$$ PV HC synapses, $$\hbox {PV}_{\text{MS-DBB}}$$ 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 $$\hbox {PV}_{\text{HC}}$$ PV HC model, the $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.

Blockade of TRPC Channels Limits Cholinergic-Driven Hyperexcitability and Seizure Susceptibility After Traumatic Brain Injury

“…Although the CA3 region demonstrated reduced AChE activity, the posttraumatic neuronal activity of CA3 pyramidal neurons was not significantly altered. We postulate that in CA3 and CA1, this is due to more pronounced inhibitory interneuron activity ( Yi et al, 2021 ) that compensates for the reduction in AChE. Evidence for this supposition includes that G q/ 11 -coupled receptors, including M 1 Rs, prime long-term potentiation at GABAergic synapses ( Morales-Weil et al, 2020 ), thus amplifying regulation of glutamatergic principal cells by cholinergic pathways.…”

Kinetics and Connectivity Properties of Parvalbumin- and Somatostatin-Positive Inhibition in Layer 2/3 Medial Entorhinal Cortex

“…Although synapses between fast-firing neurons have not been as well studied as inhibition in excitatory cells, synapses between fast firing neurons in hippocampal area CA3 (Kohus et al, 2016) and the dentate gyrus both exhibit short-term depression (Bartos et al, 2001). Similarly, synapses from Pvalb + neurons in the medial septum diagonal band of Broca (MS-DBB) onto CA1 stratum oriens interneurons and from local hippocampal Pvalb + interneurons onto CA1 pyramidal neurons both exhibit short-term depression (Yi et al, 2021). Previously, different subtypes of Pvalb + CA1 pyramidal neurons were found to have different paired pulse ratios (Maccaferri et al, 2000) in synapses onto principal cells, with the axo-axonic cell exhibiting more paired-pulse depression (PPD) than in basket cells and bistratified cells.…”

The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies

“…The intervention to MS GABAergic neurons affects theta oscillations in the MEC as well, there MS GABAergic neurons project (see section “Theta Oscillations and Cognitive Maps”). The synaptic transmission at the synapses formed between these MS GABAergic neurons and HPC GABAergic interneurons exhibits a rapid recovery of short-term depression by excitation trains, which enables highly efficient transmission at the synapses even with frequent transmissions ( Yi et al, 2021 ). The HPC to MS feedback projections via the HPC GABAergic neurons also contribute to the theta oscillations in the septo-hippocampal axis ( Kang et al, 2017 ).…”