Synergy of Glutamatergic and Cholinergic Modulation Induces Plateau Potentials in Hippocampal OLM Interneurons

Abstract

Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that are implicated in the regulation of information flow in the CA1 circuit, inhibiting cortical inputs to distal pyramidal cell dendrites, whilst disinhibiting CA3 inputs to pyramidal cells. OLM cells express metabotropic cholinergic (mAChR) and glutamatergic (mGluR) receptors, so modulation of these cells via these receptors may contribute to switching between functional modes of the hippocampus. Using a transgenic mouse line to identify OLM cells, we found that both mAChR and mGluR activation caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains. Both mAChR- and mGluR-induced plateau potentials were eliminated by blocking transient receptor potential (TRP) channels, and were dependent on intracellular calcium concentration and calcium entry. Pharmacological tests indicated that Group I mGluRs are responsible for the glutamatergic induction of plateaus. There was also a pronounced synergy between the cholinergic and glutamatergic modulation, plateau potentials being generated by agonists applied together at concentrations too low to elicit any change when applied individually. This synergy could enable OLM cells to function as coincidence detectors of different neuromodulatory systems, leading to their enhanced and prolonged activation and a functional change in information flow within the hippocampus.

Apical drive—A cellular mechanism of dreaming?

“…opposite to I h suppression via ɑARs. Recent evidence indicates that the boosting of I h via βARs dominates in neocortical layer 5 pyramidal cells (Hagger-Vaughan et al 2017;Klaus et al 2017;Hagger-Vaughan and Storm, unpublished data). Since NA and hence βAR activation is low during REM sleep, the resulting I h reduction would then reduce shunting, which may promote apical drive and dreaming, supporting our proposed mechanism of dreaming, as outlined above ( 6.3) .…”

Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex

“…During long-lasting muscarine applications, the induced depolarization (PDB) and spiking declined over time, but declined less with 10 µM than with 3 µM (Figure 2B). Whilst these PPs were clearly mAChR-dependent, PPs have been observed elsewhere to be elicited following activation of several different metabotropic receptor types (Perrier and Hounsgaard, 2003;Hagger-Vaughan and Storm, 2019;Prager et al, 2020). To test whether metabotropic glutamate receptors (mGluRs) also can induce PPs in L2/3PCs, we applied tACPD, a selective agonist of the mGluR group I/II GluRs.…”

Signal processing and computational modeling for interpretation of SEEG-recorded interictal epileptiform discharges in epileptogenic and non-epileptogenic zones

“…Lateral inhibition mediated by Martinotti cells is facilitated by cholinergic inputs [56]. In the rodent hippocampus, balanced cholinergic and mGluR activity enhances and prolongs the activation of the SST+ interneurons [57]. Moreover, depolarization of Martinotti cells by group I mGluRs has been shown in the human neocortex [58], and this mechanism has been suggested as an antiepileptic pathway.…”