title: Optimizing computer models of corticospinal neurons to replicate in vitro dynamics.
abstract: Corticospinal neurons (SPI), thick-tufted pyramidal neurons in motor cortex layer 5B that project caudally via the medullary pyramids, display distinct class-specific electrophysiological properties in vitro: strong sag with hyperpolarization, lack of adaptation, and a nearly linear frequency-current (F-I) relationship. We used our electrophysiological data to produce a pair of large archives of SPI neuron computer models in two model classes: 1) detailed models with full reconstruction; and 2) simplified models with six compartments. We used a PRAXIS and an evolutionary multiobjective optimization (EMO) in sequence to determine ion channel conductances. EMO selected good models from each of the two model classes to form the two model archives. Archived models showed tradeoffs across fitness functions. For example, parameters that produced excellent F-I fit produced a less-optimal fit for interspike voltage trajectory. Because of these tradeoffs, there was no single best model but rather models that would be best for particular usages for either single neuron or network explorations. Further exploration of exemplar models with strong F-I fit demonstrated that both the detailed and simple models produced excellent matches to the experimental data. Although dendritic ion identities and densities cannot yet be fully determined experimentally, we explored the consequences of a demonstrated proximal to distal density gradient of Ih, demonstrating that this would lead to a gradient of resonance properties with increased resonant frequencies more distally. We suggest that this dynamical feature could serve to make the cell particularly responsive to major frequency bands that differ by cortical layer.
  
  
  
  We developed models of motor cortex corticospinal neurons that replicate in vitro dynamics, including hyperpolarization-induced sag and realistic firing patterns. Models demonstrated resonance in response to synaptic stimulation, with resonance frequency increasing in apical dendrites with increasing distance from soma, matching the increasing oscillation frequencies spanning deep to superficial cortical layers. This gradient may enable specific corticospinal neuron dendrites to entrain to relevant oscillations in different cortical layers, contributing to appropriate motor output commands.
authors.affiliation: Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York; samn@neurosim.downstate.edu.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Neymotin
authors.affiliation: Department of Physiology, Northwestern University, Chicago, Illinois.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Suter
authors.affiliation: Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York.
authors.forename: Salvador
authors.initials: S
authors.lastname: Dura-Bernal
authors.affiliation: Department of Physiology, Northwestern University, Chicago, Illinois.
authors.forename: Gordon M G
authors.initials: GM
authors.lastname: Shepherd
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Migliore
authors.affiliation: Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York.|Department of Neurology, SUNY Downstate Medical Center, Brooklyn, New York.|Department of Neurology, Kings County Hospital Center, Brooklyn, New York; and.|The Robert F. Furchgott Center for Neural and Behavioral Science, Brooklyn, New York.
authors.forename: William W
authors.initials: WW
authors.lastname: Lytton
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D003198:Computer Simulation; D004558:Electric Stimulation; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques; D011712:Pyramidal Tracts / Q000166:cytology*
chemical_list: D018377:Neurotransmitter Agents
keywords: HCN channel; computer simulation; corticospinal neuron; hyperpolarization-activated cyclic nucleotide-gated channel; layer 5; motor cortex; neocortex