Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.21.306472v1?rss=1 Authors: Guet-McCreight, A., Skinner, F. K. Abstract: The wide diversity of inhibitory cells across the brain makes them fit to contribute to network dynamics in specialized fashions. However, the contributions of a particular inhibitory cell type in a behaving animal is challenging to decipher as one needs to both record cellular activities and identify the cell type being recorded. Thus, using computational modeling to explore cell-specific contributions so as to predict and hypothesize functional contributions is desirable. Here we examine potential contributions of interneuron-specific 3 (I-S3) cells - a type of inhibitory interneuron found in CA1 hippocampus that only targets other inhibitory interneurons - during simulated theta rhythms. We use previously developed multi-compartment 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 theta. We find that I-S3 cells suppress OLM cell spiking, rather than engender its spiking via post-inhibitory rebound mechanisms. To elicit recruitment similar to experiment, the inclusion of disinhibited pyramidal cell inputs is necessary, suggesting that I-S3 cell firing can broaden the window for disinhibiting pyramidal cells. Using in vivo virtual networks, we show that I-S3 cells can contribute to a sharpening of OLM cell recruitment at theta frequencies. Further, a shifting of the timing of I-S3 cell spiking due to external modulation can shift the timing of the OLM cell firing and thus disinhibitory windows. We thus propose a specialized contribution of I-S3 cells to create temporally precise coordination of modulation pathways. Copy rights belong to original authors. Visit the link for more info