Online Lecture by Frances Skinner

Translating Mechanisms from Minimal to Detailed Models of CA1 Hippocampal Microcircuits to Understand the Generation of Theta Rhythms

Using mathematical models to obtain a cellular-based understanding of how our brains work is challenging because of multiple cell types, the details associated with them, and deciding what mathematical representation to use in building the network models. To tackle this, we have brought together previously published minimal and detailed models of CA1 microcircuitry that generate intra-hippocampal LFP theta (3-12 Hz) rhythms. The minimal model uses an Izhikevich cellular structure and only includes fast-firing parvalbumin-positive interneurons and pyramidal cells, whereas the detailed model includes eight different inhibitory cell types and pyramidal cells that have a multi-compartment conductance-based structure. We hypothesize an ‘inhibition-based tuning’ mechanism using the minimal model, and comparisons between minimal and detailed models lead to an expansive and principled exploration of the detailed model that allows this to be explored. We find that the detailed model supports such a mechanism with the theta rhythm being initiated by the pyramidal cell population and regularized by the inhibitory cell populations, and further shows a strong correlation between the theta frequency and the net input being received by the pyramidal cells. Overall, our work shows that linking minimal and detailed models with a clear biological context allows a translation of mechanisms from minimal to detailed models to be obtained. This leads to a cellular-based foundation from which a full understanding of theta generation in the hippocampus can be built.

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