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

• Published in: eNeuro 2024-07, Vol.11 (7), p.ENEURO.0190-24.2024
• Main Authors: Upchurch, Carol M, Knowlton, Christopher J, Chamberland, Simon, Canavier, Carmen C
• Format: Article
• Language: English
• Subjects: 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; New Research; Parvalbumins - metabolism; Pyramidal Cells - metabolism; Pyramidal Cells - physiology; Shaker Superfamily of Potassium Channels - metabolism
• ISSN: 2373-2822; 2373-2822
• DOI: 10.1523/ENEURO.0190-24.2024

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 K 1 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 K 1 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 K 1 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 K 1, 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, K 1 inactivation.