Non-uniform dendritic distributions of Ihchannels in experimentally-derived multi-compartment models of oriens-lacunosum/moleculare hippocampal interneurons

Abstract

Inhibitory interneurons are crucial for generating prominent network rhythms and coordinating information flow in hippocampal microcircuits. The oriens-lacunosum/moleculare (O-LM) cell is an interneuron type in the hippocampal CA1 region that synapses onto distal dendrites of pyramidal cells [1]. O-LM cells mediate feedback inhibition onto pyramidal cells and gate information flow between sensory input from entorhinal cortex and previously stored associations from the CA3 area. Despite the distal location of inhibitory synapses from O-LM cells onto the excitatory populations, their control of pyramidal cell output has been clearly shown [2]. Thus, how the dynamic firing properties of O-LM cells in its network circuit environment is generated needs to be understood. Furthermore, it is clear that the presence and distribution of voltage-gated channels on the dendrites of O-LM cells would affect its integrative properties in response to synaptic input. However, given the highly challenging aspects to experimentally determine whether and what sort of distributions of voltage-gated channels are present on dendrites, we take advantage of computational modeling studies to consider different possibilities. In this work, we focus on Ih channels. While the existence of Ih channels in O-LM cells has long been known [3], it is at present unknown whether these channels are present on O-LM cell dendrites. In previous work, we used ensemble modeling techniques in conjunction with experimental data to show that physiologically realistic multi-compartment O-LM cell models may possess dendritic Ih, but only uniform distributions across the dendritic tree were examined. In the work here, we turned our focus to how the kinetics of Ih and non-uniform distributions would affect our models’ output. In tuning our models, we found that different Ih kinetics as well as non-uniform distributions were better able to reproduce experimental O-LM cell responses. Interestingly, this occurred only when there were decreasing conductance densities away from the soma. This is in contrast to pyramidal cells which have higher Ih conductance densities in more distal dendrites [4]. Non-uniform distributions of Ih would indicate that there are particular synaptic input distributions that affect the firing properties of O-LM cells and thus their ability to affect information flow.