Cortical Interneuron & Pyramidal Cell Model of Cortical Spreading Depression (Stein & Harris 2022)

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This 2-cell cortical circuit model consists of a negative feedback loop between a single compartment pyramidal cell and a single compartment interneuron. Ion concentrations in the extra- and intracellular spaces are included in the model. The model is used to test the contribution of cortical inhibitory interneurons to the initiation of cortical spreading depression, as characterized by spike block in the pyramidal cell. Results show that interneuronal inhibition provides a wider dynamic range to the circuit and generally improves stability against spike block. Despite these beneficial effects, strong interneuronal firing contributed to rapidly changing extracellular ion concentrations, which facilitated hyperexcitation and led to spike block first in the interneuron and then in the pyramidal cell. The model results demonstrate that while the role of interneurons in cortical microcircuits is complex, they are critical to the initiation of pyramidal cell spike block and CSD. See reference below for more details.
1 . Stein W, Harris AL (2022) Interneuronal dynamics facilitate the initiation of spike block in cortical microcircuits Journal of Computational Neuroscience [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Realistic Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s):
Gap Junctions:
Receptor(s): GabaA; Glutamate;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: FORTRAN;
Model Concept(s): Spreading depression;
Search NeuronDB for information about:  GabaA; Glutamate; Gaba; Glutamate;
0.				!ti (ms); initial time for simulation
70000.				!tf (ms); final time for simulation
-70.				!V0 (mV); initial membrane potential PYRAMIDAL NEURON 
0.	1.	0.		!n0, h0,  Ca0; initial conditions for activation functions PYRAMIDAL NEURON
140.	5.			!K_i0,	K_o0 (mM); initial intracellular potassium, initial extracellular potassium PYRAMIDAL NEURON
12.	140.			!Na_i0,	Na_o0 (mM); initial intracellular sodium, initial extracellular sodium PYRAMIDAL NEURON
5.	119.			!Cl_i0,	Cl_o0 (mM); initial intracellular chloride, initial extracellular chloride PYRAMIDAL NEURON
0.	0.	0.		!lils0, lilse0, lilsi0; initial conditions for synaptic functions (for gaba to pyramidal, self-excitatory glutamate, glutamate to interneuron)
-70.				!V0_int (mV); initial membrane potential INTERNEURON 
0.	1.			!n0_int,h0_int; initial conditions for activation functions INTERNEURON 
145.3				!K_i0_int; initial intracellular potassium INTERNEURON 
17.9				!Na_i0_int; initial intracellular sodium INTERNEURON
2400010				!Nstep; number of time steps for Runge-Kutta ODE solver 
0.65				!gami; Conversion factor between current density and rate of ion concentration change 
0.4	0.4	0.1		!ggabastart,ggabaend,ggabastep (mS/cm^2); loop over gaba conductance from ggabastart to ggabaend in steps of ggabastep
3.	3.	1.0		!Jestart, Jeend, Jestep (microA); loop over PYRAMIDAL NEURON injected current from Jestart to Jeend in steps of Jestep
1.	1.	0.2		!Ji_intstart, Ji_intend, Ji_intstep (microA); loop over INTERNEURON injected current from Ji_intstart to Ji_intend in steps of Ji_intstep
1				!write membrane potentials? 1=yes, 0=no

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