Chrna2-OLM interneurons display different membrane properties and h-current magnitude depending on dorsoventral location

Hippocampus. 2019 Dec;29(12):1224-1237. doi: 10.1002/hipo.23134. Epub 2019 Jul 13.

Abstract

The hippocampus is an extended structure displaying heterogeneous anatomical cell layers along its dorsoventral axis. It is known that dorsal and ventral regions show different integrity when it comes to functionality, innervation, gene expression, and pyramidal cell properties. Still, whether hippocampal interneurons exhibit different properties along the dorsoventral axis is not known. Here, we report electrophysiological properties of dorsal and ventral oriens lacunosum moleculare (OLM) cells from coronal sections of the Chrna2-cre mouse line. We found dorsal OLM cells to exhibit a significantly more depolarized resting membrane potential compared to ventral OLM cells, while action potential properties were similar between the two groups. We found ventral OLM cells to show a higher initial firing frequency in response to depolarizing current injections but also to exhibit a higher spike-frequency adaptation than dorsal OLM cells. Additionally, dorsal OLM cells displayed large membrane sags in response to negative current injections correlating with our results showing that dorsal OLM cells have more hyperpolarization-activated current (Ih ) compared to ventral OLM cells. Immunohistochemical examination indicates the h-current to correspond to hyperpolarization-activated cyclic nucleotide-gated subunit 2 (HCN2) channels. Computational studies suggest that Ih in OLM cells is essential for theta oscillations in hippocampal circuits, and here we found dorsal OLM cells to present a higher membrane resonance frequency than ventral OLM cells. Thus, our results highlight regional differences in membrane properties between dorsal and ventral OLM cells allowing this interneuron to differently participate in the generation of hippocampal theta rhythms depending on spatial location along the dorsoventral axis of the hippocampus.

Keywords: Chrna2-cre; H-resonance; HCN; OLM cell; dorsoventral; hyperpolarization-activated current; septotemporal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Female
  • Hippocampus / physiology*
  • Interneurons / physiology*
  • Male
  • Membrane Potentials / physiology*
  • Mice
  • Mice, Transgenic
  • Receptors, Nicotinic / physiology*

Substances

  • CHRNA2 protein, mouse
  • Receptors, Nicotinic