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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.

Ferguson KA, Huh CY, Amilhon B, Manseau F, Williams S, Skinner FK - Front Syst Neurosci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada.

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.

No MeSH data available.


Model interneurons recapitulate spiking behavior of experimentally recorded interneurons during intrinsically generated theta in vitro. (A) Example one second trace of PV+ cell model firing (top) during the EPSCPV input (bottom). (B) Same as in (A) but for an OLM interneuron model.
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Figure 7: Model interneurons recapitulate spiking behavior of experimentally recorded interneurons during intrinsically generated theta in vitro. (A) Example one second trace of PV+ cell model firing (top) during the EPSCPV input (bottom). (B) Same as in (A) but for an OLM interneuron model.

Mentions: While both PV+ and SOM+ cells showed tendencies to fire slightly before theta peaks, our SOM+ cells (n = 9) on average fired 5.32 ms closer to its LFP peak compared to the PV+ cells (n = 8). Thus, we input EPSCOLM 5.32 ms later than EPSCPV. To capture the experimental variability in amplitude and timing of EPSCs across cells, we varied the gain (factor by which the EPSC was scaled to alter the amplitude) and timing of the EPSCs across cells with a normal distribution (gain standard deviation: 0.12 for EPSCOLM, 0.21 for EPSCPV; timing standard deviation: 3.5 ms for EPSCOLM, 6.6 ms for EPSCPV), in accordance with our experimental recordings. In this way, each cell model received a unique set of excitatory synaptic inputs reflecting the range of amplitudes and timing of those recorded experimentally. In Figure 6 we show example traces of the experimental data, demonstrating PV+ and SOM+ cell firing during an endogenous LFP theta oscillation. We compare this with Figure 7, demonstrating that our cell models fire similarly to the experimental cells when driven with the scaled EPSCPV and EPSCOLM inputs.


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

Ferguson KA, Huh CY, Amilhon B, Manseau F, Williams S, Skinner FK - Front Syst Neurosci (2015)

Model interneurons recapitulate spiking behavior of experimentally recorded interneurons during intrinsically generated theta in vitro. (A) Example one second trace of PV+ cell model firing (top) during the EPSCPV input (bottom). (B) Same as in (A) but for an OLM interneuron model.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4528165&req=5

Figure 7: Model interneurons recapitulate spiking behavior of experimentally recorded interneurons during intrinsically generated theta in vitro. (A) Example one second trace of PV+ cell model firing (top) during the EPSCPV input (bottom). (B) Same as in (A) but for an OLM interneuron model.
Mentions: While both PV+ and SOM+ cells showed tendencies to fire slightly before theta peaks, our SOM+ cells (n = 9) on average fired 5.32 ms closer to its LFP peak compared to the PV+ cells (n = 8). Thus, we input EPSCOLM 5.32 ms later than EPSCPV. To capture the experimental variability in amplitude and timing of EPSCs across cells, we varied the gain (factor by which the EPSC was scaled to alter the amplitude) and timing of the EPSCs across cells with a normal distribution (gain standard deviation: 0.12 for EPSCOLM, 0.21 for EPSCPV; timing standard deviation: 3.5 ms for EPSCOLM, 6.6 ms for EPSCPV), in accordance with our experimental recordings. In this way, each cell model received a unique set of excitatory synaptic inputs reflecting the range of amplitudes and timing of those recorded experimentally. In Figure 6 we show example traces of the experimental data, demonstrating PV+ and SOM+ cell firing during an endogenous LFP theta oscillation. We compare this with Figure 7, demonstrating that our cell models fire similarly to the experimental cells when driven with the scaled EPSCPV and EPSCOLM inputs.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Fundamental Neurobiology, Toronto Western Research Institute, University Health Network Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada.

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.

No MeSH data available.