Persistent Interruption in Parvalbumin-Positive Inhibitory Interneurons: Biophysical and Mathematical Mechanisms

eNeuro. 2024 Jul 9;11(7):ENEURO.0190-24.2024. doi: 10.1523/ENEURO.0190-24.2024. Print 2024 Jul.

Abstract

Persistent activity in excitatory pyramidal cells (PYRs) is a putative mechanism for maintaining memory traces during working memory. We have recently demonstrated persistent interruption of firing in fast-spiking parvalbumin-expressing interneurons (PV-INs), a phenomenon that could serve as a substrate for persistent activity in PYRs through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs. Modeling and mathematical analysis showed that the slowly inactivating potassium current KV1 contributes to type 2 excitability, enables the multiple firing regimes observed experimentally in PV-INs, and provides a mechanism for robust persistent interruption of firing. Using a fast/slow separation of times scales approach with the KV1 inactivation variable as a bifurcation parameter shows that the initial inhibitory stimulus stops repetitive firing by moving the membrane potential trajectory onto a coexisting stable fixed point corresponding to a nonspiking quiescent state. As KV1 inactivation decays, the trajectory follows the branch of stable fixed points until it crosses a subcritical Hopf bifurcation (HB) and then spirals out into repetitive firing. In a model describing entorhinal cortical PV-INs without KV1, interruption of firing could be achieved by taking advantage of the bistability inherent in type 2 excitability based on a subcritical HB, but the interruption was not robust to noise. Persistent interruption of firing is therefore broadly applicable to PV-INs in different brain regions but is only made robust to noise in the presence of a slow variable, KV1 inactivation.

Keywords: KV1; fast-spiking interneuron; hippocampus; persistent activity.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / physiology
  • Entorhinal Cortex / metabolism
  • Entorhinal Cortex / physiology
  • Interneurons* / metabolism
  • Interneurons* / physiology
  • Male
  • Models, Neurological*
  • Neural Inhibition / physiology
  • Parvalbumins* / metabolism
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology
  • Shaker Superfamily of Potassium Channels / metabolism

Substances

  • Parvalbumins
  • Shaker Superfamily of Potassium Channels