Network models provide insights into how oriens-lacunosum-moleculare and bistratified cell interactions influence the power of local hippocampal CA1 theta oscillations.

Katie A Ferguson,Sylvain Williams,Carey Y L Huh,Bénédicte Amilhon,Frances K Skinner,Frédéric Manseau

doi:10.3389/fnsys.2015.00110

Abstract

Hippocampal theta is a 4–12 Hz rhythm associated with episodic memory, and although it has been studied extensively, the cellular mechanisms underlying its generation are unclear. The complex interactions between different interneuron types, such as those between oriens–lacunosum-moleculare (OLM) interneurons and bistratified cells (BiCs), make their contribution to network rhythms difficult to determine experimentally. We created network models that are tied to experimental work at both cellular and network levels to explore how these interneuron interactions affect the power of local oscillations. Our cellular models were constrained with properties from patch clamp recordings in the CA1 region of an intact hippocampus preparation in vitro. Our network models are composed of three different types of interneurons: parvalbumin-positive (PV+) basket and axo-axonic cells (BC/AACs), PV+ BiCs, and somatostatin-positive OLM cells. Also included is a spatially extended pyramidal cell model to allow for a simplified local field potential representation, as well as experimentally-constrained, theta frequency synaptic inputs to the interneurons. The network size, connectivity, and synaptic properties were constrained with experimental data. To determine how the interactions between OLM cells and BiCs could affect local theta power, we explored how the number of OLM-BiC connections and connection strength affected local theta power. We found that our models operate in regimes that could be distinguished by whether OLM cells minimally or strongly affected the power of network theta oscillations due to balances that, respectively, allow compensatory effects or not. Inactivation of OLM cells could result in no change or even an increase in theta power. We predict that the dis-inhibitory effect of OLM cells to BiCs to pyramidal cell interactions plays a critical role in the resulting power of network theta oscillations. Overall, our network models reveal a dynamic interplay between different classes of interneurons in influencing local theta power.

Highlights

IntroductionThe prominent local field potential (LFP) theta rhythm (4–12 Hz) is observed in mammals in a variety of brain structures (e.g., the hippocampus, the prefrontal cortex, the subicular complex, the entorhinal cortex, the amygdala), and is most robustly recorded from the CA1 region of the hippocampus (Buzsáki, 2002)
The prominent local field potential (LFP) theta rhythm (4–12 Hz) is observed in mammals in a variety of brain structures, and is most robustly recorded from the CA1 region of the hippocampus (Buzsáki, 2002)
We note that the peak frequency will not change, since we are imposing a theta oscillation of a fixed frequency on the interneurons through the experimentally derived excitatory postsynaptic current (EPSC) drive (EPSCPV and EPSCOLM for PV+ and oriens– lacunosum-moleculare (OLM) cells respectively)

Summary

Introduction

The prominent local field potential (LFP) theta rhythm (4–12 Hz) is observed in mammals in a variety of brain structures (e.g., the hippocampus, the prefrontal cortex, the subicular complex, the entorhinal cortex, the amygdala), and is most robustly recorded from the CA1 region of the hippocampus (Buzsáki, 2002). Neuronal firing patterns throughout the brain are correlated with hippocampal theta rhythms (Chrobak and Buzsáki, 1998; Dickson et al, 2003; Pape et al, 2005; Mizuseki et al, 2009; van der Meer and Redish, 2011), and globally, theta is often thought to be strongly influenced by hippocampal theta (Battaglia et al, 2011) This hippocampal theta rhythm is thought to play a lead role in spatial navigation and episodic memory (Buzsáki, 2002), and is recorded from the hippocampus during rapid eye movement (REM) sleep and voluntary behaviors such as exploration. A number of different inhibitory (GABAergic) interneuron types may be involved in local hippocampal oscillations (Klausberger and Somogyi, 2008), and how critical each cell type is to rhythm generation and to the power of different frequencies is yet to be determined These interneuron types exhibit a wide diversity of morphologies, synaptic targets, and firing properties (Freund and Buzsáki, 1996; McBain and Fisahn, 2001). We focus on theta power and two major interneuron groups: oriens– lacunosum-moleculare (OLM) interneurons and parvalbuminpositive (PV+) interneurons

Methods

Results

Conclusion