Modeling Reveals Human–Rodent Differences in H-Current Kinetics Influencing Resonance in Cortical Layer 5 Neurons

Author:

Rich Scott1,Moradi Chameh Homeira1,Sekulic Vladislav1,Valiante Taufik A12345,Skinner Frances K16

Affiliation:

1. Division of Clinical and Computational Neuroscience, Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada

2. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 1A1, Canada

3. Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A1, Canada

4. Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada

5. Electrical and Computer Engineering, University of Toronto, Toronto, ON M5S 1A1, Canada

6. Departments of Medicine (Neurology) and Physiology, University of Toronto, Toronto, ON M5S 1A1, Canada

Abstract

Abstract While our understanding of human neurons is often inferred from rodent data, inter-species differences between neurons can be captured by building cellular models specifically from human data. This includes understanding differences at the level of ion channels and their implications for human brain function. Thus, we here present a full spiking, biophysically detailed multi-compartment model of a human layer 5 (L5) cortical pyramidal cell. Model development was primarily based on morphological and electrophysiological data from the same human L5 neuron, avoiding confounds of experimental variability. Focus was placed on describing the behavior of the hyperpolarization-activated cation (h-) channel, given increasing interest in this channel due to its role in pacemaking and differentiating cell types. We ensured that the model exhibited post-inhibitory rebound spiking considering its relationship with the h-current, along with other general spiking characteristics. The model was validated against data not used in its development, which highlighted distinctly slower kinetics of the human h-current relative to the rodent setting. We linked the lack of subthreshold resonance observed in human L5 neurons to these human-specific h-current kinetics. This work shows that it is possible and necessary to build human-specific biophysical neuron models in order to understand human brain dynamics.

Funder

Natural Sciences and Engineering Research Council of Canada

Krembil Foundation

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Cognitive Neuroscience

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