Hyperexcitability from Nav1.2 channel loss in neocortical pyramidal cells (Spratt et al accepted)

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Accession:267067
Based on the Layer 5 thick-tufted pyramidal cell from the Blue Brain Project, we modify the distribution of the sodium channel Nav1.2 to recapitulate an increase in excitability observed in ex vivo slice experiments.
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Prefrontal cortex (PFC);
Cell Type(s): Neocortex layer 5 pyramidal cell;
Channel(s): I h; I M; I Potassium; I Sodium; I L high threshold; I T low threshold;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.2 SCN2A;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s):
Implementer(s): Ben-Shalom, Roy [rbenshalom at ucdavis.edu]; Kyoung, Henry [hkyoung at berkeley.edu];
Search NeuronDB for information about:  I L high threshold; I T low threshold; I M; I h; I Sodium; I Potassium;
/
SprattEtAl2021
Na12 Analysis
.ipynb_checkpoints
mechanisms
morphology
params
Stims
Volts
README *
.provenance.json *
axon_utils.hoc
biophysics.hoc *
cellinfo.json *
constants.hoc *
creategui.hoc *
createsimulation.hoc *
fit.hoc *
gui.ses *
init.hoc *
LICENSE *
morphology.hoc *
mosinit.hoc *
NaV12_analysis.ipynb *
ringplot.hoc *
run.py *
run_RmpRiTau.py *
runModel.hoc *
template.hoc *
topo_code.hoc *
                            

/*
Copyright (c) 2015 EPFL-BBP, All rights reserved.

THIS SOFTWARE IS PROVIDED BY THE BLUE BRAIN PROJECT ``AS IS''
AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO,
THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR
PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE BLUE BRAIN PROJECT
BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR
CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF
SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR
BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY,
WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE
OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN
IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.

This work is licensed under a
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
To view a copy of this license, visit
http://creativecommons.org/licenses/by-nc-sa/4.0/legalcode or send a letter to
Creative Commons,
171 Second Street, Suite 300,
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*/

/*
 * @file biophys.hoc
 * @brief Biophysics
 * @author Etay Hay, Werner Van Geit @ BBP
 * @date 2015
*/
begintemplate cADpyr232_biophys
public biophys, distribute

proc distribute(){local x localobj sl
        strdef stmp,distfunc,mech
        sl = $o1
        mech = $s2
        distfunc = $s3
        sprint(distfunc,"%%s %s(%%f) = %s",mech, distfunc)
        forsec sl for(x) {
            sprint (stmp,distfunc,secname(),x,distance(x))
            execute(stmp)
        }
    }

proc biophys() {
	forsec $o1.basal {
		insert Ih
		
	}

	forsec $o1.apical {
		insert Im
		insert NaTs2_t
		insert SKv3_1
		insert Ih
		insert na12
		insert na12mut
		insert na16
		gbar_na12 =0
		gbar_na12mut =0
		gbar_na16=0
	}

	forsec $o1.somatic {
		insert Ca_HVA
		insert SKv3_1
		insert SK_E2
		insert Ca_LVAst
		insert Ih
		insert NaTs2_t
		insert CaDynamics_E2
		insert na12
		insert na12mut
		insert na16
		gbar_na12 =0
		gbar_na12mut =0
		gbar_na16=0

	}

	forsec $o1.axonal {
		insert Ca_HVA
		insert SKv3_1
		insert SK_E2
		insert CaDynamics_E2
		insert Nap_Et2
		insert K_Pst
		insert K_Tst
		insert Ca_LVAst
		insert NaTa_t
		insert na12
		insert na12mut
		insert na16
		gbar_na12 = 0
		gbar_na12mut = 0
		gbar_na16 = 0
	}

	forsec $o1.all {
		insert pas
	}

	forsec $o1.all {
		e_pas = -75 
	}

	forsec $o1.all {
		Ra = 100 
	}

	forsec $o1.all {
		cm = 1 
	}

	forsec $o1.all {
		g_pas = 3e-5 
	}

	forsec $o1.apical {
		ena = 50 
	}

	forsec $o1.apical {
		ek = -85 
	}

	forsec $o1.apical {
		cm = 2 
	}

	forsec $o1.axonal {
		ena = 50 
	}

	forsec $o1.axonal {
		ek = -85 
	}

	forsec $o1.basal {
		cm = 2 
	}

	forsec $o1.somatic {
		ena = 50 
	}

	forsec $o1.somatic {
		ek = -85 
	}

		distribute($o1.basal,"gIhbar_Ih","(0.0 * %g + 1.0)*0.000080")
		distribute($o1.apical,"gNaTs2_tbar_NaTs2_t","(0.0 * %g + 1.0)*0.026145")
		distribute($o1.apical,"gSKv3_1bar_SKv3_1","(0.0 * %g + 1.0)*0.004226")
		distribute($o1.apical,"gIhbar_Ih","(-0.869600 + 2.087000*exp((%g-0.000000)*0.003100))*0.000110")
		distribute($o1.apical,"gImbar_Im","(0.0 * %g + 1.0)*0.000143")
		distribute($o1.axonal,"gNaTa_tbar_NaTa_t","(0.0 * %g + 1.0)*3.137968")
		distribute($o1.axonal,"gK_Tstbar_K_Tst","(0.0 * %g + 1.0)*0.089259")
		distribute($o1.axonal,"gamma_CaDynamics_E2","(0.0 * %g + 1.0)*0.002910")
		distribute($o1.axonal,"gNap_Et2bar_Nap_Et2","(0.0 * %g + 1.0)*0.006827")
		distribute($o1.axonal,"gSK_E2bar_SK_E2","(0.0 * %g + 1.0)*0.007104")
		distribute($o1.axonal,"gCa_HVAbar_Ca_HVA","(0.0 * %g + 1.0)*0.000990")
		distribute($o1.axonal,"gK_Pstbar_K_Pst","(0.0 * %g + 1.0)*0.973538")
		distribute($o1.axonal,"gSKv3_1bar_SKv3_1","(0.0 * %g + 1.0)*1.021945")
		distribute($o1.axonal,"decay_CaDynamics_E2","(0.0 * %g + 1.0)*287.198731")
		distribute($o1.axonal,"gCa_LVAstbar_Ca_LVAst","(0.0 * %g + 1.0)*0.008752")
		distribute($o1.somatic,"gamma_CaDynamics_E2","(0.0 * %g + 1.0)*0.000609")
		distribute($o1.somatic,"gSKv3_1bar_SKv3_1","(0.0 * %g + 1.0)*0.303472")
		distribute($o1.somatic,"gSK_E2bar_SK_E2","(0.0 * %g + 1.0)*0.008407")
		distribute($o1.somatic,"gCa_HVAbar_Ca_HVA","(0.0 * %g + 1.0)*0.000994")
		distribute($o1.somatic,"gNaTs2_tbar_NaTs2_t","(0.0 * %g + 1.0)*0.983955")
		distribute($o1.somatic,"gIhbar_Ih","(0.0 * %g + 1.0)*0.000080")
		distribute($o1.somatic,"decay_CaDynamics_E2","(0.0 * %g + 1.0)*210.485284")
		distribute($o1.somatic,"gCa_LVAstbar_Ca_LVAst","(0.0 * %g + 1.0)*0.000333")
		
		
		        
		forsec $o1.all {
		g_pas = 7.120456108418522658e-06
		//e_pas = -1.354672766109964641e+02
		e_pas = -100
		}
	forsec $o1.axonal{
		gNaTa_tbar_NaTa_t =  2.944996928407823589e+01 
		gK_Tstbar_K_Tst = 7.057598347931356431e-01
		gNap_Et2bar_Nap_Et2 = 5.474034057879299114e-02
		gK_Pstbar_K_Pst = 2.995607833249227525e+00
		gSKv3_1bar_SKv3_1 = 1.795864927118776766e+00 
		gCa_LVAstbar_Ca_LVAst = 1.376286159287454106e-03
		gCa_HVAbar_Ca_HVA = 1.181439489922307830e-04
	}
	forsec $o1.somatic{
		gSKv3_1bar_SKv3_1 = 8.396194779331378477e-02
		gCa_HVAbar_Ca_HVA = 3.124468461012596082e-04
		gNaTs2_tbar_NaTs2_t = 4.163647845421887261e-01
		gCa_LVAstbar_Ca_LVAst =  1.514478001521781143e-02
		
	}
	
		
		
}


endtemplate cADpyr232_biophys