Deciphering how interneuron specific 3 cells control oriens lacunosum-moleculare cells to contribute to circuit function

J Neurophysiol. 2021 Oct 1;126(4):997-1014. doi: 10.1152/jn.00204.2021. Epub 2021 Aug 11.


The wide diversity of inhibitory cells across the brain makes them suitable to contribute to network dynamics in specialized fashions. However, the contributions of a particular inhibitory cell type in a behaving animal are challenging to untangle as one needs to both record cellular activities and identify the cell type being recorded. Thus, using computational modeling and theory to predict and hypothesize cell-specific contributions is desirable. Here, we examine potential contributions of interneuron-specific 3 (I-S3) cells-an inhibitory interneuron found in CA1 hippocampus that only targets other inhibitory interneurons-during simulated θ rhythms. We use previously developed multicompartment models of oriens lacunosum-moleculare (OLM) cells, the main target of I-S3 cells, and explore how I-S3 cell inputs during in vitro and in vivo scenarios contribute to θ. We find that I-S3 cells suppress OLM cell spiking, rather than engender its spiking via postinhibitory rebound mechanisms, and contribute to θ frequency spike resonance during simulated in vivo scenarios. To elicit recruitment similar to in vitro experiments, inclusion of disinhibited pyramidal cell inputs is necessary, implying that I-S3 cell firing broadens the window for pyramidal cell disinhibition. Using in vivo virtual networks, we show that I-S3 cells contribute to a sharpening of OLM cell recruitment at θ frequencies. Furthermore, shifting the timing of I-S3 cell spiking due to external modulation shifts the timing of the OLM cell firing and thus disinhibitory windows. We propose a specialized contribution of I-S3 cells to create temporally precise coordination of modulation pathways.NEW & NOTEWORTHY How information is processed across different brain structures is an important question that relates to the different functions that the brain performs. Using modeling and theoretical analyses, we show that an inhibitory cell type that only inhibits other inhibitory cells can broaden the window for disinhibition of excitatory cells, manage input pathway switching, and modulate inhibitory cell spiking. This work contributes to the knowledge of how coordination between sensory and memory consolidation information can be attained.

Keywords: dendrites; hippocampus; interneuron; ion channels; simulation.

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / physiology*
  • Computer Simulation
  • Interneurons / physiology*
  • Models, Biological*
  • Nerve Net / physiology*
  • Pyramidal Cells / physiology*
  • Theta Rhythm / physiology*