Internal KCN: On the generation of theta rhythms in the hippocampus

This is a practice talk for the Final Supervisory Committee Meeting

Thesis Title: On the generation of theta rhythms in the hippocampus

Thesis Abstract: 

A prevalent local field potential (LFP) rhythm in the CA1 hippocampus associated with memory processing and spatial navigation is the theta (3-12 Hz) oscillation. Theta rhythms emerge intrinsically in an in vitro whole hippocampus preparation. This system makes it possible to assess the contribution of different cell types, a problem that remains unresolved, in the absence of state-dependent confounding factors typically encountered in vivo.

To decipher the theta generation mechanism we leverage insights from minimal models in application to biologically detailed ones. We extract a piece of a previously published full CA1 model, the the segment model, on which we test minimal model hypotheses. We distinguish the pyramidal (PYR) cells as the theta rhythm initiators whose activity is regularized by inhibitory cells supporting an ‘inhibition-based tuning’ mechanism. We find a strong correlation between the PYR cell input currents and the resulting theta frequency, establishing that the intrinsic PYR cell properties underpin frequency char acteristics. We analyze contributions of external drives and find that strongest theta responses are generated by the hippocampus CA3 while weakest responses are induced by inputs from the CA1. Subsequently we turn our attention to the full CA1 model and explain the theta activities it produces according to our gathered insights. We demonstrate that the termination of PYR cell theta bursts relies on sequential activation of distinct inhibitory cell classes.

Two main types of inhibitory cells have been considered particularly important for the generation of theta rhythms, the parvalbumin-positive (PV+) and the somatostatin-positive (SOM+) cells. Having demonstrated the importance of PV+ cells in theta generation, we turn to the SOM+ oriens lacunosum-moleculare (OLM) cells, a heavily studied cell class whose role is still unclear. We find that OLM cells regulate the robustness of the LFP laminar polarity profile without affecting average power, a robust response that depends on co-activation of distal inhibition and basal excitation. Finally, we estimate the spatial extent of the theta LFP, and predict that about 22,000 PYR cells participate in intrinsic theta generation. The work presented in this thesis provides a cellular-based foundation from which in vivo theta activities can be explored.