Long-Term Inactivation of Na+ Channels as a Mech of Adaptation in CA1 Pyr Cells (Upchurch et al '22)


"... Ramps were applied to CA1 pyramidal neurons from male rats in vitro (slice electrophysiology) and in silico (multi-compartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared to somatic ramps. We incorporated a four-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in closed states, which comprise the available pool..."

Model Type: Neuron or other electrically excitable cell

Region(s) or Organism(s): Hippocampus

Cell Type(s): Hippocampus CA1 pyramidal GLU cell

Currents: I K,Ca; I Calcium; I L high threshold; I R; I T low threshold; I h; I_KD; I K; I M; I Potassium; I Sodium

Receptors: NMDA

Genes: Nav1.6 SCN8A

Model Concept(s): Place cell/field

Simulation Environment: NEURON

References:

Upchurch CM et al. (2022). Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Cells The Journal of neuroscience : the official journal of the Society for Neuroscience. 42 [PubMed]


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