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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.


The two experimental O-LM cell somatic membrane potential traces used in the optimization work. Somatic membrane voltage response to a −90 pA hyperpolarizing current injection step for two experimental O-LM cells: cell 4525#4 (blue) and cell 4610#2 (red). Horizontal black bar shows time of application of −90 pA current injection step.
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Figure 3: The two experimental O-LM cell somatic membrane potential traces used in the optimization work. Somatic membrane voltage response to a −90 pA hyperpolarizing current injection step for two experimental O-LM cells: cell 4525#4 (blue) and cell 4610#2 (red). Horizontal black bar shows time of application of −90 pA current injection step.

Mentions: The optimizations were performed using a subset of the experimental data used in Sekulić et al. (2014) and described in detail in Lawrence et al. (2006b). Specifically, −90 pA somatic current steps of duration of 1 s from two different O-LM cells were used (Figure 3). The starting voltage before the hyperpolarizing step was −74 mV and for each optimization, the bias, or holding current required to set this voltage was specified within the optimization itself since the amount of current required varies depending on the passive properties and Gh, which are parameters that were optimized as well.


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)

The two experimental O-LM cell somatic membrane potential traces used in the optimization work. Somatic membrane voltage response to a −90 pA hyperpolarizing current injection step for two experimental O-LM cells: cell 4525#4 (blue) and cell 4610#2 (red). Horizontal black bar shows time of application of −90 pA current injection step.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The two experimental O-LM cell somatic membrane potential traces used in the optimization work. Somatic membrane voltage response to a −90 pA hyperpolarizing current injection step for two experimental O-LM cells: cell 4525#4 (blue) and cell 4610#2 (red). Horizontal black bar shows time of application of −90 pA current injection step.
Mentions: The optimizations were performed using a subset of the experimental data used in Sekulić et al. (2014) and described in detail in Lawrence et al. (2006b). Specifically, −90 pA somatic current steps of duration of 1 s from two different O-LM cells were used (Figure 3). The starting voltage before the hyperpolarizing step was −74 mV and for each optimization, the bias, or holding current required to set this voltage was specified within the optimization itself since the amount of current required varies depending on the passive properties and Gh, which are parameters that were optimized as well.

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.