Limits...
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.


Boxplots of the dendritic scaling factor kd and total Gh membrane conductance across different model morphologies and dendritic Gh distributions. (A) Statistics pertaining to the scaling factor, or kd, of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the kd values for each category. (B) Statistics pertaining to the total Gh membrane conductance (in nS) of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the total Gh values for each category.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4343010&req=5

Figure 9: Boxplots of the dendritic scaling factor kd and total Gh membrane conductance across different model morphologies and dendritic Gh distributions. (A) Statistics pertaining to the scaling factor, or kd, of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the kd values for each category. (B) Statistics pertaining to the total Gh membrane conductance (in nS) of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the total Gh values for each category.

Mentions: We next addressed the distributions of h-channels in our models by examining the fitted dendritic scaling factors, or kd values, for the models of both morphologies and non-uniform dendritic distributions—linear or sigmoidal—and fixed baseline Gh (Figure 9A). The medians of the kd values were negative for models with morphology 1 (−0.8409 for linear, n = 6, and −1.4605 for sigmoidal distributions, n = 4) and positive for models with morphology 2 (0.1454 for linear, n = 5, and 0.0138 for sigmoidal distributions, n = 4), using both experimental traces in the optimizations in each case.


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)

Boxplots of the dendritic scaling factor kd and total Gh membrane conductance across different model morphologies and dendritic Gh distributions. (A) Statistics pertaining to the scaling factor, or kd, of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the kd values for each category. (B) Statistics pertaining to the total Gh membrane conductance (in nS) of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the total Gh values for each category.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Boxplots of the dendritic scaling factor kd and total Gh membrane conductance across different model morphologies and dendritic Gh distributions. (A) Statistics pertaining to the scaling factor, or kd, of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the kd values for each category. (B) Statistics pertaining to the total Gh membrane conductance (in nS) of models with optimized Rm, Cm, t1, t2, …, t8, and dendritic scaling factor kd for both linear and sigmoidal dendritic distribution for Gh against both experimental traces used. Red lines indicate the median; box edges denote the 25th and 75th percentiles; whiskers extend to the extremes of the total Gh values for each category.
Mentions: We next addressed the distributions of h-channels in our models by examining the fitted dendritic scaling factors, or kd values, for the models of both morphologies and non-uniform dendritic distributions—linear or sigmoidal—and fixed baseline Gh (Figure 9A). The medians of the kd values were negative for models with morphology 1 (−0.8409 for linear, n = 6, and −1.4605 for sigmoidal distributions, n = 4) and positive for models with morphology 2 (0.1454 for linear, n = 5, and 0.0138 for sigmoidal distributions, n = 4), using both experimental traces in the optimizations in each case.

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.