Alexandra Pierri Chatzikalymniou 1,2, Frances K. Skinner 1,3,2
1 Krembil Research Institute, University Health Network
2 Department of Physiology, University of Toronto
3 Department of Medicine (Neurology), University of Toronto
Abstract
Oscillations in LFPs commonly occur and analyses of them fuel brain function hypotheses. An understanding of the cellular correlates and pathways affecting LFPs is needed but many overlapping pathways in vivo makes this difficult to achieve. A prevalent LFP rhythm in the hippocampus that is associated with episodic memory and spatial navigation is the (3-12 Hz) ‘theta’ oscillation. Theta rhythms emerge intrinsically in an in vitro whole hippocampus preparation and are produced by local interactions between interneurons and pyramidal (PYR) cells. Overlapping pathways are much reduced in this preparation making it possible to decipher the contribution of different cell types to LFP generation. We focus on oriens-lacunosum/moleculare (OLM) cells as a major class of interneurons in the hippocampus. OLM cells can influence PYR cells through two distinct pathways, (i) by direct inhibition of PYR cell distal dendrites, and (ii) by indirect disinhibition of PYR cell proximal dendrites by inhibiting bistratified cells (BiCs) that target them. We use previous inhibitory network models and build biophysical LFP models using volume conductor theory. Performing 1000’s of simulations via high-performance computing, we assess the effect of OLM cells to ongoing intrinsic LFP theta rhythms by directly comparing our model LFP features with experiment. We find that robust LFP theta responses adhering to reproducible experimental criteria occur only for particular connectivities between OLM cells and BiCs. Decomposition of the LFP reveals that OLM cell inputs onto the PYR cell regulate robustness of LFP responses without affecting average power and that the robust response depends on co-activation of distal inhibition and basal excitation. We estimate the spatial extent of the region generating LFP theta rhythms and predict that approximately 22,000 PYR cells participate in theta rhythm generation. Our understanding of OLM cells’ contributions to intrinsic theta rhythms can drive hypothesis developments of their contributions in vivo.