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Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during in vivo-like states.
F1000Res. 2020; 9:180.F

Abstract

Background:

Despite technological advances, how specific cell types are involved in brain function remains shrouded in mystery. Further, little is known about the contribution of different ion channel currents to cell excitability across different neuronal subtypes and their dendritic compartments in vivo. The picture that we do have is largely based on somatic recordings performed in vitro. Uncovering dendritic ion channel current contributions in neuron subtypes that represent a minority of the neuronal population is not currently a feasible task using purely experimental means.

Methods:

We employ two morphologically-detailed multi-compartment models of a specific type of inhibitory interneuron, the oriens lacunosum moleculare (OLM) cell. The OLM cell is a well-studied cell type in CA1 hippocampus that is important in gating sensory and contextual information. We create in vivo-like states for these cellular models by including levels of synaptic bombardment that would occur in vivo. Using visualization tools and analyses we assess the ion channel current contribution profile across the different somatic and dendritic compartments of the models.

Results:

We identify changes in dendritic excitability, ion channel current contributions and co-activation patterns between in vitro and in vivo-like states. Primarily, we find that the relative timing between ion channel currents are mostly invariant between states, but exhibit changes in magnitudes and decreased propagation across dendritic compartments. We also find enhanced dendritic hyperpolarization-activated cyclic nucleotide-gated channel (h-channel) activation during in vivo-like states, which suggests that dendritically located h-channels are functionally important in altering signal propagation in the behaving animal.

Conclusions:

Overall, we have demonstrated, using computational modelling, the dynamical changes that can occur to ion channel mechanisms governing neuronal spiking. Simultaneous access to dendritic compartments during simulated in vivo states shows that the magnitudes of some ion channel current contributions are differentially altered during in vivo-like states relative to in vitro.

Authors+Show Affiliations

Krembil Research Institute, University Health Network, Toronto, ON, M5T 0S8, Canada. Department of Physiology, University of Toronto, Toronto, ON, Canada.Krembil Research Institute, University Health Network, Toronto, ON, M5T 0S8, Canada. Departments of Medicine (Neurology) and Physiology, University of Toronto, Toronto, ON, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32595950

Citation

Guet-McCreight, Alexandre, and Frances K. Skinner. "Computationally Going Where Experiments Cannot: a Dynamical Assessment of Dendritic Ion Channel Currents During in Vivo-like States." F1000Research, vol. 9, 2020, p. 180.
Guet-McCreight A, Skinner FK. Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during in vivo-like states. F1000Res. 2020;9:180.
Guet-McCreight, A., & Skinner, F. K. (2020). Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during in vivo-like states. F1000Research, 9, 180. https://doi.org/10.12688/f1000research.22584.2
Guet-McCreight A, Skinner FK. Computationally Going Where Experiments Cannot: a Dynamical Assessment of Dendritic Ion Channel Currents During in Vivo-like States. F1000Res. 2020;9:180. PubMed PMID: 32595950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during in vivo-like states. AU - Guet-McCreight,Alexandre, AU - Skinner,Frances K, Y1 - 2020/03/11/ PY - 2020/06/08/accepted PY - 2020/7/1/entrez KW - Hippocampus KW - computational neuroscience KW - dendrites KW - interneuron KW - ion channels KW - synapses. SP - 180 EP - 180 JF - F1000Research JO - F1000Res VL - 9 N2 - Background: Despite technological advances, how specific cell types are involved in brain function remains shrouded in mystery. Further, little is known about the contribution of different ion channel currents to cell excitability across different neuronal subtypes and their dendritic compartments in vivo. The picture that we do have is largely based on somatic recordings performed in vitro. Uncovering dendritic ion channel current contributions in neuron subtypes that represent a minority of the neuronal population is not currently a feasible task using purely experimental means. Methods: We employ two morphologically-detailed multi-compartment models of a specific type of inhibitory interneuron, the oriens lacunosum moleculare (OLM) cell. The OLM cell is a well-studied cell type in CA1 hippocampus that is important in gating sensory and contextual information. We create in vivo-like states for these cellular models by including levels of synaptic bombardment that would occur in vivo. Using visualization tools and analyses we assess the ion channel current contribution profile across the different somatic and dendritic compartments of the models. Results: We identify changes in dendritic excitability, ion channel current contributions and co-activation patterns between in vitro and in vivo-like states. Primarily, we find that the relative timing between ion channel currents are mostly invariant between states, but exhibit changes in magnitudes and decreased propagation across dendritic compartments. We also find enhanced dendritic hyperpolarization-activated cyclic nucleotide-gated channel (h-channel) activation during in vivo-like states, which suggests that dendritically located h-channels are functionally important in altering signal propagation in the behaving animal. Conclusions: Overall, we have demonstrated, using computational modelling, the dynamical changes that can occur to ion channel mechanisms governing neuronal spiking. Simultaneous access to dendritic compartments during simulated in vivo states shows that the magnitudes of some ion channel current contributions are differentially altered during in vivo-like states relative to in vitro. SN - 2046-1402 UR - https://www.unboundmedicine.com/medline/citation/32595950/Computationally_going_where_experiments_cannot:_a_dynamical_assessment_of_dendritic_ion_channel_currents_during_in_vivo-like_states L2 - https://f1000research.com/articles/10.12688/f1000research.22584.2/doi DB - PRIME DP - Unbound Medicine ER -
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