Multitarget pharmacology for Dystonia in M1 (Neymotin et al 2016)


" ... We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. ..."

Model Type: Realistic Network; Molecular Network

Region(s) or Organism(s): Neocortex

Cell Type(s): Neocortex L5/6 pyramidal GLU cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex V1 interneuron basket PV GABA cell; Neocortex fast spiking (FS) interneuron; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron; Neocortex layer 4 neuron; Neocortex layer 2-3 interneuron; Neocortex layer 4 interneuron; Neocortex layer 5 interneuron; Neocortex layer 6a interneuron

Currents: I A; I h; I_SERCA; Ca pump; I K,Ca; I Calcium; I L high threshold; I T low threshold; I N; I_KD; I M; I Na,t

Receptors: GabaA; GabaB; AMPA; mGluR

Genes: HCN1

Transmitters: Gaba; Glutamate

Model Concept(s): Oscillations; Activity Patterns; Beta oscillations; Reaction-diffusion; Calcium dynamics; Pathophysiology; Multiscale

Simulation Environment: NEURON; Python

Implementer(s): Neymotin, Sam [Samuel.Neymotin at nki.rfmh.org]; Dura-Bernal, Salvador [salvadordura at gmail.com]

References:

Neymotin SA, Dura-Bernal S, Lakatos P, Sanger TD, Lytton WW. (2016). Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex. Frontiers in pharmacology. 7 [PubMed]


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