Effects of Chloride accumulation and diffusion on GABAergic transmission (Jedlicka et al 2011)

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Accession:148253
"In the CNS, prolonged activation of GABA(A) receptors (GABA(A)Rs) has been shown to evoke biphasic postsynaptic responses, consisting of an initial hyperpolarization followed by a depolarization. A potential mechanism underlying the depolarization is an acute chloride (Cl(-)) accumulation resulting in a shift of the GABA(A) reversal potential (E(GABA)). The amount of GABA-evoked Cl(-) accumulation and accompanying depolarization depends on presynaptic and postsynaptic properties of GABAergic transmission, as well as on cellular morphology and regulation of Cl(-) intracellular concentration ([Cl(-)](i)). To analyze the influence of these factors on the Cl(-) and voltage behavior, we studied spatiotemporal dynamics of activity-dependent [Cl(-)](i) changes in multicompartmental models of hippocampal cells based on realistic morphological data. ..."
Reference:
1 . Jedlicka P, Deller T, Gutkin BS, Backus KH (2011) Activity-dependent intracellular chloride accumulation and diffusion controls GABA(A) receptor-mediated synaptic transmission. Hippocampus 21:885-98 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Extracellular;
Brain Region(s)/Organism:
Cell Type(s): Dentate gyrus granule GLU cell;
Channel(s): I Chloride; I_HCO3;
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Influence of Dendritic Geometry; Short-term Synaptic Plasticity; Chloride regulation;
Implementer(s): Jedlicka, Peter [jedlicka at em.uni-frankfurt.de]; Mohapatra, Namrata [mohapatra at em.uni-frankfurt.de];
Search NeuronDB for information about:  Dentate gyrus granule GLU cell; GabaA; I Chloride; I_HCO3; Gaba;
// ----------------------------------------------------------------------------
// membrane.hoc
// loads the full cell morphology, inserts passive
// membrane properties, corrects membrane resistance
// and capacitance for spines, and corrects (roughly) 
// for temperature if needed
//
// 2007-06-17, Christoph Schmidt-Hieber, University of Freiburg
//
// accompanies the publication:
// Schmidt-Hieber C, Jonas P, Bischofberger J (2007)
// Subthreshold Dendritic Signal Processing and Coincidence Detection 
// in Dentate Gyrus Granule Cells. J Neurosci 27:8430-8441
//
// send bug reports and suggestions to christoph.schmidt-hieber@uni-freiburg.de
//
// 2007-08-31: adheres to NetworkReadyCell policy
//
// ----------------------------------------------------------------------------

// load gui or stdrun:
load_file("stdrun.hoc")

load_file("./../share/genutils.hoc")
load_file("./../share/calcSpines.hoc")
load_file("./../share/fixnseg.hoc")

begintemplate cell_8

public is_art
public init, topol, basic_shape, subsets, geom, biophys, geom_nseg, biophys_inhomo
public synlist, x, y, z, position, connect2target
public somaLoc,distalDendLoc,proxDendLoc,synDendLoc,spineCount,n_sections,n_axon
public section
public all,den,axo

external verbose,debug_mode,accuracy,calc_spines
external q10_cm,q10_g_pas,q10_Ra,tempScale,geom_nseg_shared,lambda_f

objref somaLoc,distalDendLoc,proxDendLoc,synDendLoc,spineCount,this,synlist

proc init() {
	topol()
	if (debug_mode) print "Loaded cell, n_sections=",n_sections
	subsets()
	geom()
	biophys()
	geom_nseg()
	synlist = new List()
	synapses()
	x = y = z = 0 // only change via position
	n_sections = 0
	n_axon = 0
}

// dummy compartments, will be updated later:
create section[1]

proc init_spines() {
	forall insert spines
        section[0] count_spines = 0.0 * L
        section[12] count_spines = 2/section[12].L * L
        section[13] count_spines = 5/section[13].L * L
        section[15] count_spines = 14/section[15].L * L
        section[19] count_spines = 38/16.637 * L
        section[20] count_spines = 96/48.980 * L
        section[21] count_spines = 103/section[21].L * L
        section[22] count_spines = 34/section[22].L * L
        section[23] count_spines = 62/25.970 * L
        section[16] count_spines = 52/23.755 * L
        section[17] count_spines = 40/15.524 * L
        section[18] count_spines = 76/33.565 * L
        section[14] count_spines = 7/section[14].L * L
        section[24] count_spines = 8/section[24].L * L
        section[25] count_spines = 12/11.6 * L
        section[26] count_spines = 44/16.154 * L
        section[27] count_spines = 19/section[27].L * L
        section[28] count_spines = 65/21.461 * L
        section[29] count_spines = 53/23.280 * L
        section[30] count_spines = 39/21.965 * L
        section[31] count_spines = 34/15.807 * L
        section[32] count_spines = 48/24.158 * L
        section[33] count_spines = 20/section[33].L * L
        section[34] count_spines = 58/28.65 * L
        section[35] count_spines = 30/16.693 * L
        section[36] count_spines = 37/19.037 * L
        section[1] count_spines = 12/section[1].L * L
        section[7] count_spines = 6/section[7].L * L
        section[8] count_spines = 46/24.365 * L
        section[9] count_spines = 91/40.419 * L
        section[10] count_spines = 89/46.571 * L
        section[11] count_spines = 65/27.148 * L
        section[2] count_spines = 48/25.486 * L
        section[3] count_spines = 104/37.486 * L
        section[4] count_spines = 24/11.161 * L
        section[5] count_spines = 80/37.177 * L
        section[6] count_spines = 80/37.177 * L
	forall calc_spines()
}

proc init_pas() {
	forall {
		insert pas
		//e_pas=0
		e_pas=-80
		cm = 1.13955 * tempScale(q10_cm) * scale_spines
		g_pas = 2.79596e-05 * tempScale(q10_g_pas) * scale_spines
		Ra = 191.446 * tempScale(q10_Ra)
	}
}

proc basic_shape() {localobj morphoFile
	strdef sectionLabel
	morphoFile = new File()
	morphoFile.ropen("./cell_8/morpho.txt")
	n_sections = morphoFile.scanvar()
	
	create section[n_sections]
	n_axon = morphoFile.scanvar()
	forall pt3dclear()
	while (!morphoFile.eof()) {
		morphoFile.scanstr(sectionLabel)
		if (strcmp(sectionLabel,"S")==0) { 
			section[morphoFile.scanvar()] pt3dadd(morphoFile.scanvar(),morphoFile.scanvar(),morphoFile.scanvar(),morphoFile.scanvar())
		} else {
			print "Unknown section label, aborting file import"
			return
		}
	}
	morphoFile.close()
	// define soma:
	section[0]  somaLoc = new Location(0.5)
	// define dendritic sites:
	section[3] distalDendLoc = new Location(0.8)
	section[2] proxDendLoc = new Location(0.05)
	section[23] synDendLoc = new Location(0.8)

	access somaLoc.secRef.sec
}

proc topol() {
	basic_shape()

        connect section[1](0.0), section[0](1.0)
        connect section[2](0.0), section[1](1.0)
        connect section[3](0.0), section[2](1.0)
        connect section[4](0.0), section[2](1.0)
        connect section[5](0.0), section[4](1.0)
        connect section[6](0.0), section[4](1.0)
        connect section[7](0.0), section[1](1.0)
        connect section[8](0.0), section[7](1.0)
        connect section[9](0.0), section[8](1.0)
        connect section[10](0.0), section[8](1.0)
        connect section[11](0.0), section[7](1.0)
        connect section[12](0.0), section[0](1.0)
        connect section[13](0.0), section[12](1.0)
        connect section[14](0.0), section[13](1.0)
        connect section[15](0.0), section[13](1.0)
        connect section[16](0.0), section[15](1.0)
        connect section[17](0.0), section[16](1.0)
        connect section[18](0.0), section[16](1.0)
        connect section[19](0.0), section[15](1.0)
        connect section[20](0.0), section[19](1.0)
        connect section[21](0.0), section[20](1.0)
        connect section[22](0.0), section[20](1.0)
        connect section[23](0.0), section[19](1.0)
        connect section[24](0.0), section[12](1.0)
        connect section[25](0.0), section[24](1.0)
        connect section[26](0.0), section[25](1.0)
        connect section[27](0.0), section[25](1.0)
        connect section[28](0.0), section[27](1.0)
        connect section[29](0.0), section[27](1.0)
        connect section[30](0.0), section[24](1.0)
        connect section[31](0.0), section[30](1.0)
        connect section[32](0.0), section[31](1.0)
        connect section[33](0.0), section[31](1.0)
        connect section[34](0.0), section[33](1.0)
        connect section[35](0.0), section[33](1.0)
        connect section[36](0.0), section[30](1.0)

	init_spines()
}

objref all,den,axo
proc subsets() { local i
  objref all,den,axo
  all = new SectionList()
    for i=0, n_sections-1 section[i] all.append()
  den = new SectionList()
    for i=1, n_sections-1 section[i] den.append()
  axo = new SectionList()
}

proc geom() {
}

proc geom_nseg() {
	geom_nseg_shared()
	// increase nseg even further (tribute to Josef):
	if (accuracy >= 1) {
		forall nseg*=3
	}
}

proc biophys() {
	init_pas()
}

proc biophys_inhomo(){}

proc position() { local i
  somaLoc.secRef.sec for i = 0, n3d()-1 {
    pt3dchange(i, $1-x+x3d(i), $2-y+y3d(i), $3-z+z3d(i), diam3d(i))
  }
  x = $1  y = $2  z = $3
}

obfunc connect2target() { localobj nc //$o1 target point process, optional $o2 returned NetCon
  section[0] nc = new NetCon(&v(0), $o1)
  nc.threshold = 10
  if (numarg() == 2) { $o2 = nc } // for backward compatibility
  return nc
}

objref syn_
proc synapses() {
}

func is_art() { return 0 }

endtemplate cell_8



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