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]
Citations  Citation Browser
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_1

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
}

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

proc init_spines() {
	forall insert spines
        section[0] scale_spines = 1
        section[1] scale_spines = 1
        section[2] scale_spines = 1.411094934
        section[3] scale_spines = 1.416883748
        section[4] scale_spines = 1.729047321
        section[5] scale_spines = 2.069020426
        section[6] scale_spines = 2.326445289
        section[7] scale_spines = 2.240566878
        section[8] scale_spines = 2.247047065
        section[9] scale_spines = 1.587543094
        section[10] scale_spines = 2.176976844
        section[11] scale_spines = 2.306580816
        section[12] scale_spines = 2.465495602
        section[13] scale_spines = 2.302641477
        section[14] scale_spines = 1.578706329
        section[15] scale_spines = 2.281395846
        section[16] scale_spines = 2.723287111
        section[17] scale_spines = 2.592732622
        section[18] scale_spines = 2.057561119
        section[19] scale_spines = 2.607937017
        section[20] scale_spines = 2.290552402
        section[21] scale_spines = 1.400969731
        section[22] scale_spines = 1.838412712
        section[23] scale_spines = 1.477322919
        section[24] scale_spines = 1.601159698
        section[25] scale_spines = 2.083591581
        section[26] scale_spines = 2.141902991
        section[27] scale_spines = 2.209160604
        section[28] scale_spines = 2.066909863
        section[29] scale_spines = 1.680521809
        section[30] scale_spines = 2.387833318
        section[31] scale_spines = 2.053749875
        section[32] scale_spines = 2.754637153
        section[33] scale_spines = 2.584118369
        section[34] scale_spines = 1
}

proc init_pas() {
	forall {
		insert pas
		e_pas=0
		cm = 0.893279 * tempScale(q10_cm) * scale_spines
		g_pas = 2.54178e-05 * tempScale(q10_g_pas) * scale_spines
		Ra = 225.066 * tempScale(q10_Ra)
	}
}

proc basic_shape() {localobj morphoFile
	strdef sectionLabel
	morphoFile = new File()
	morphoFile.ropen("./cell_1/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[8] distalDendLoc = new Location(0.8)
	section[3] proxDendLoc = new Location(0.05)
	section[27] synDendLoc = new Location(0.8)

	access somaLoc.secRef.sec

}

proc topol() {
	basic_shape()

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

	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 if (i != 34) section[i] den.append()
  axo = new SectionList()
    section[34] axo.append()
}

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[34] 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_1