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

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          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.

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          Most cited references41

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          Simple model of spiking neurons.

          A model is presented that reproduces spiking and bursting behavior of known types of cortical neurons. The model combines the biologically plausibility of Hodgkin-Huxley-type dynamics and the computational efficiency of integrate-and-fire neurons. Using this model, one can simulate tens of thousands of spiking cortical neurons in real time (1 ms resolution) using a desktop PC.
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            Theta oscillations in the hippocampus.

            Theta oscillations represent the "on-line" state of the hippocampus. The extracellular currents underlying theta waves are generated mainly by the entorhinal input, CA3 (Schaffer) collaterals, and voltage-dependent Ca(2+) currents in pyramidal cell dendrites. The rhythm is believed to be critical for temporal coding/decoding of active neuronal ensembles and the modification of synaptic weights. Nevertheless, numerous critical issues regarding both the generation of theta oscillations and their functional significance remain challenges for future research.
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              Interneurons of the hippocampus.

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                Author and article information

                Contributors
                Journal
                Front Syst Neurosci
                Front Syst Neurosci
                Front. Syst. Neurosci.
                Frontiers in Systems Neuroscience
                Frontiers Media S.A.
                1662-5137
                07 August 2015
                2015
                : 9
                : 110
                Affiliations
                [1] 1Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network Toronto, ON, Canada
                [2] 2Department of Physiology, University of Toronto Toronto, ON, Canada
                [3] 3Department of Psychiatry, Douglas Mental Health University Institute, McGill University Montreal, QC, Canada
                [4] 4Departments of Medicine (Neurology) and Physiology, University of Toronto Toronto, ON, Canada
                Author notes

                Edited by: Vassilis Cutsuridis, Foundation for Research and Technology - Hellas, Greece

                Reviewed by: Bruce Graham, University of Stirling, UK; Satish S. Nair, University of Missouri, USA

                *Correspondence: Katie A. Ferguson, Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network, Krembil Discovery Tower, Toronto Western Hospital, 60 Leonard Avenue, 7KD410, Toronto, ON M5T 2S8, Canada katie.ferguson@ 123456utoronto.ca
                Article
                10.3389/fnsys.2015.00110
                4528165
                26300744
                107440f7-eb4a-4e93-9c79-2172fbabaeb0
                Copyright © 2015 Ferguson, Huh, Amilhon, Manseau, Williams and Skinner.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 April 2015
                : 14 July 2015
                Page count
                Figures: 14, Tables: 3, Equations: 7, References: 56, Pages: 20, Words: 14927
                Funding
                Funded by: Canadian Institutes of Health Research (CIHR)
                Award ID: MOP-102573
                Funded by: Natural Sciences and Engineering Research Canada (NSERC)
                Award ID: RGPIN-203700
                Funded by: Ontario Graduate Scholarship (OGS)
                Funded by: Canada Foundation
                Funded by: Government of Ontario
                Funded by: Ontario Research Fund Research Excellence
                Funded by: University of Toronto
                Categories
                Neuroscience
                Original Research

                Neurosciences
                mathematical model,inhibitory networks,theta rhythm,interneuron,computational model,hippocampus,microcircuit

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