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Dendritic distributions of I h channels in experimentally-derived multi-compartment models of oriens-lacunosum/moleculare (O-LM) hippocampal interneurons.

Sekulić V, Chen TC, Lawrence JJ, Skinner FK - Front Synaptic Neurosci (2015)

Bottom Line: We found that the best O-LM models that included uniformly distributed h-channels in the dendrites could not fully capture the "sag" response.In tuning our models, we found that different kinetics and non-uniform distributions could better reproduce experimental O-LM cell responses.Although the present results were morphology-dependent, our work shows that it should be possible to determine the distributions and characteristics of O-LM cells with recordings and morphologies from the same cell.

View Article: PubMed Central - PubMed

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

ABSTRACT
The O-LM cell type mediates feedback inhibition onto hippocampal pyramidal cells and gates information flow in the CA1. Its functions depend on the presence of voltage-gated channels (VGCs), which affect its integrative properties and response to synaptic input. Given the challenges associated with determining densities and distributions of VGCs on interneuron dendrites, we take advantage of computational modeling to consider different possibilities. In this work, we focus on hyperpolarization-activated channels (h-channels) in O-LM cells. While h-channels are known to be present in O-LM cells, it is unknown whether they are present on their dendrites. In previous work, we used ensemble modeling techniques with experimental data to obtain insights into potentially important conductance balances. We found that the best O-LM models that included uniformly distributed h-channels in the dendrites could not fully capture the "sag" response. This led us to examine activation kinetics and non-uniform distributions of h-channels in the present work. In tuning our models, we found that different kinetics and non-uniform distributions could better reproduce experimental O-LM cell responses. In contrast to CA1 pyramidal cells where higher conductance densities of h-channels occur in more distal dendrites, decreasing conductance densities of h-channels away from the soma were observed in O-LM models. Via an illustrative scenario, we showed that having dendritic h-channels clearly speeds up back-propagating action potentials in O-LM cells, unlike when h-channels are present only in the soma. Although the present results were morphology-dependent, our work shows that it should be possible to determine the distributions and characteristics of O-LM cells with recordings and morphologies from the same cell. We hypothesize that h-channels are distributed in O-LM cell dendrites and endow them with particular synaptic integration properties that shape information flow in hippocampus.

No MeSH data available.


Related in: MedlinePlus

O-LM model response to −90 pA hyperpolarizing current changes when all active voltage-gated channels, except Ih, are blocked. Somatic voltage traces in response to a −90 pA current injection step for experimental cell 4525#4 (solid red), optimized model R4 with all ion channels active (solid black) and optimized model R4 with only Ih active, with other channels blocked (dashed black).
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Figure 7: O-LM model response to −90 pA hyperpolarizing current changes when all active voltage-gated channels, except Ih, are blocked. Somatic voltage traces in response to a −90 pA current injection step for experimental cell 4525#4 (solid red), optimized model R4 with all ion channels active (solid black) and optimized model R4 with only Ih active, with other channels blocked (dashed black).

Mentions: Although other currents in O-LM cells were not blocked when applying the −90 pA current injection step, it is clear that other currents would have made some contribution, though it was expected to be minimal in the voltage range given by this current step regime. We demonstrate this by plotting the steady-state activation curves for all currents in the model (Figure 6A), which clearly shows that Ih is the predominantly active current in the voltage range present with −90pA steps. Furthermore, this is dynamically shown when plotting the current flows through the various voltage-dependent ion channels in the models (Figure 6B), where it is clear that the main active current during the 1 s-long duration of −90pA protocol was Ih, starting from 181 ms into the virtual experiment. It is because of this that we were able to take advantage of the existing set of data to do the computational explorations of Ih distributions here. To illustrate this, we blocked all of the currents except for Ih in one of the models. As shown in Figure 7, this produced a small change only in the resulting somatic voltage trace with the −90 pA hyperpolarizing current injection protocol.


Dendritic distributions of I h channels in experimentally-derived multi-compartment models of oriens-lacunosum/moleculare (O-LM) hippocampal interneurons.

Sekulić V, Chen TC, Lawrence JJ, Skinner FK - Front Synaptic Neurosci (2015)

O-LM model response to −90 pA hyperpolarizing current changes when all active voltage-gated channels, except Ih, are blocked. Somatic voltage traces in response to a −90 pA current injection step for experimental cell 4525#4 (solid red), optimized model R4 with all ion channels active (solid black) and optimized model R4 with only Ih active, with other channels blocked (dashed black).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4343010&req=5

Figure 7: O-LM model response to −90 pA hyperpolarizing current changes when all active voltage-gated channels, except Ih, are blocked. Somatic voltage traces in response to a −90 pA current injection step for experimental cell 4525#4 (solid red), optimized model R4 with all ion channels active (solid black) and optimized model R4 with only Ih active, with other channels blocked (dashed black).
Mentions: Although other currents in O-LM cells were not blocked when applying the −90 pA current injection step, it is clear that other currents would have made some contribution, though it was expected to be minimal in the voltage range given by this current step regime. We demonstrate this by plotting the steady-state activation curves for all currents in the model (Figure 6A), which clearly shows that Ih is the predominantly active current in the voltage range present with −90pA steps. Furthermore, this is dynamically shown when plotting the current flows through the various voltage-dependent ion channels in the models (Figure 6B), where it is clear that the main active current during the 1 s-long duration of −90pA protocol was Ih, starting from 181 ms into the virtual experiment. It is because of this that we were able to take advantage of the existing set of data to do the computational explorations of Ih distributions here. To illustrate this, we blocked all of the currents except for Ih in one of the models. As shown in Figure 7, this produced a small change only in the resulting somatic voltage trace with the −90 pA hyperpolarizing current injection protocol.

Bottom Line: We found that the best O-LM models that included uniformly distributed h-channels in the dendrites could not fully capture the "sag" response.In tuning our models, we found that different kinetics and non-uniform distributions could better reproduce experimental O-LM cell responses.Although the present results were morphology-dependent, our work shows that it should be possible to determine the distributions and characteristics of O-LM cells with recordings and morphologies from the same cell.

View Article: PubMed Central - PubMed

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

ABSTRACT
The O-LM cell type mediates feedback inhibition onto hippocampal pyramidal cells and gates information flow in the CA1. Its functions depend on the presence of voltage-gated channels (VGCs), which affect its integrative properties and response to synaptic input. Given the challenges associated with determining densities and distributions of VGCs on interneuron dendrites, we take advantage of computational modeling to consider different possibilities. In this work, we focus on hyperpolarization-activated channels (h-channels) in O-LM cells. While h-channels are known to be present in O-LM cells, it is unknown whether they are present on their dendrites. In previous work, we used ensemble modeling techniques with experimental data to obtain insights into potentially important conductance balances. We found that the best O-LM models that included uniformly distributed h-channels in the dendrites could not fully capture the "sag" response. This led us to examine activation kinetics and non-uniform distributions of h-channels in the present work. In tuning our models, we found that different kinetics and non-uniform distributions could better reproduce experimental O-LM cell responses. In contrast to CA1 pyramidal cells where higher conductance densities of h-channels occur in more distal dendrites, decreasing conductance densities of h-channels away from the soma were observed in O-LM models. Via an illustrative scenario, we showed that having dendritic h-channels clearly speeds up back-propagating action potentials in O-LM cells, unlike when h-channels are present only in the soma. Although the present results were morphology-dependent, our work shows that it should be possible to determine the distributions and characteristics of O-LM cells with recordings and morphologies from the same cell. We hypothesize that h-channels are distributed in O-LM cell dendrites and endow them with particular synaptic integration properties that shape information flow in hippocampus.

No MeSH data available.


Related in: MedlinePlus