Glutamatergic and cholinergic metabotropic modulation induces plateau potentials in hippocampal OLM interneurons

Abstract

Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that have been implicated in regulation of information flow and synaptic plasticity in the CA1 circuit. Since anatomical evidence indicate that OLM cells express metabotopic cholinergic (mAChR) and glutamatergic (mGluR) receptors, such modulation of these cells may contribute to switching between functional modes of the hippocampus. Using a transgenic mouse line to identify the Chrna2-positive OLM cells, we investigated metabotropic neuromodulation of intrinsic properties of OLM cells. We found that both mAChR and mGluR activation increased the spontaneous action potential rate and caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains. Both the mAChR- and mGluR-induced increased spontaneous firing rate and plateau potentials were dependent on intracellular calcium, and were eliminated by blocking Ca2+-dependent transient receptor potential (TRP) cation channels. At the receptor level, Group I mGluRs were found to be responsible for the glutamatergic modulation of the plateau potentials. There was also a pronounced synergy between the cholinergic and glutamatergic modulation of the plateau potentials. Our findings provide insights into how OLM cells are modulated by different neurotransmitters, and are likely to have functional implications on how OLM cells regulate hippocampal information processing during different brain states.