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;
//For passive properties
REVERSAL_PAS = -70
//Mario Vuksic's in vivo data (44µm IML/OML border)
IML_border = actCell.somaLoc.secRef.sec.L/2+44	


forsec actCell.all {e_pas=REVERSAL_PAS}
//reminder: all,den,axo are lists of all, dendritic and axonal sections, respectively

forall {

    insert cldifus
    cli0_cldifus = 5
    clo0_cldifus = 133.5
    celsius = 35
}

PREL  = 0.18			// Phco3/Pcl relative permeability

DISTAL_SIMULATION = 0		// 0 for simulation of a centric dendritic synapse
DIAM_SIMULATION = 0
DIAM = 2
//For synaptic parameters, see Schmidt-Hieber et al. JN 2007; Santhakumar et al. J Neurophysiol 2005, Table 4

TAU1 = 0.5	//dendritic HC-GC synapse, Santhakumar et al. 2005
TAU2 = 6	//dendritic HC-GC synapse, Santhakumar et al. 2005
G = 0.0005
VARIANCE_G = 0

NOISE = 1		//0 no noise
STIMINTERVAL=25	//one event in X s
printf("Stim. frequency: %g Hz.\n",1000/STIMINTERVAL)

STIMNUMBER=1e9		//unlimited source of mPSCs
STIMSTART=0

TSTOP=5000


// Creating objects and procedures for inserting synaptic inputs
//artificial presynaptic compartment for stimulation
create presynapse	
access presynapse
{diam=0.01 L=0.01
insert cldifus
cli0_cldifus = 5
clo0_cldifus = 133.5}	
	
objref list_of_Locations
list_of_Locations = new List()

objref list_of_synapses
list_of_synapses = new List()

objref list_of_presynapses
list_of_presynapses = new List()

objref list_of_netcons
list_of_netcons = new List()

objref list_of_synLocations
list_of_synLocations = new List()

proc createInput() {
	$o1 = new gaba($2)
	$o1.tau1 = TAU1 	//ms
	$o1.tau2 = TAU2 	//ms
	$o1.P = PREL
	list_of_synapses.append($o1)
}


proc createStim() {
	access presynapse
	$o1 = new NetStim($2)
	$o1.start = STIMSTART	//ms
	$o1.number = STIMNUMBER 	
	$o1.interval = STIMINTERVAL	//ms
	$o1.noise = NOISE
	$o1.seed($3)		//to begin each simulation round (for a cell) with a different NetStim seed
	list_of_presynapses.append($o1)
}

//initiating random number generator
ropen("/proc/uptime")		// get a seed  that is changing based on the processing time
	{			
 		rseed = fscan()		// so that simulation will not start with the same seed
		ropen()		
	}
objref random
random = new Random(rseed)

//creating list of locations (path from a selected distal dendrite to soma)
	
actCell.somaLoc.secRef.sec distance(0,actCell.somaLoc.loc)
actCell.synDendLoc.secRef.sec {
	maxLength=distance(1.0)
}

centricdistance=maxLength/2
printf("Centric distance from soma: %f\n",centricdistance)

// Walk from distal dendrite to center of soma:
actCell.synDendLoc.secRef.sec list_of_Locations = pathToRootCenter()

//determine location for a synapse
objref dist_from_center
dist_from_center = new Vector()

objref dist_from_center2
dist_from_center2 = new Vector()

for i=0,list_of_Locations.count()-1 {
	list_of_Locations.o(i).secRef.sec {
				dist_from_center.append(abs(list_of_Locations.o(i).distToRootCenter-centricdistance))
	}
}

i=dist_from_center.min_ind()
printf("Index for the centric location: %f\n",i)

//changing the diameter of the dendrite

if (DIAM_SIMULATION == 1)  {
	for i=0,list_of_Locations.count()-1 {
		list_of_Locations.o(i).secRef.sec {
			if (issection(".*section[0]")) {} else {list_of_Locations.o(i).secRef.sec.diam = DIAM}		
			printf("The dendritic diameter at the rec. site %f is:  %f\n",i,list_of_Locations.o(i).secRef.sec.diam)	
		}	
	}
i=0
	
}

//procedure for creating lists of synaptic objects

proc create_synapses()  {local i, j, k, node  	localobj syn, stim, syncon, tempLoc, helplist	
	if (DISTAL_SIMULATION == 1)  {
		printf("Want to simulate a distal synapse because DISTAL_SIMULATION is: %d\n",DISTAL_SIMULATION)
		actCell.synDendLoc.secRef.sec  {
						node = (2*nseg-1)/(2*nseg)
						printf("Number of segments and the node: %f\n",nseg)
					    printf("Number of node: %f\n",node)
					    printf("Number of node: %f\n",node)
						tempLoc = new Location(node)
						createInput(syn, tempLoc.loc)
						createStim(stim, 0.5, rseed)
						syncon = new NetCon(list_of_presynapses.o(0), list_of_synapses.o(0), 0, 0, G)
						list_of_netcons.append(syncon)		//list_of_netcons = netcon.synlist(list_of_netcons)
						list_of_synLocations.append(tempLoc)
						/*
						printf("Distal synapse has been created %d um from soma (%g nS, %g ms, %g ms.)\n",list_of_synLocations.o(0).distToRootCenter, 1000*G, TAU1, TAU2)
						printf("Dendritic diameter at the syn. location: %g um.", list_of_synLocations.o(0).secRef.sec.diam(node))
						*/
		}
	} 
	if (DISTAL_SIMULATION == 0)  {
		helplist = new List()
		printf("Want to simulate a centric synapse because DISTAL_SIMULATION is: %d\n",DISTAL_SIMULATION)
		i = dist_from_center.min_ind()
		list_of_Locations.o(i).secRef.sec {
					for j = 0, nseg-1 {			//looking for the node to insert the centric synapse
							node = (2*(j+1)-1)/(2*nseg)
							tempLoc = new Location(node)
							helplist.append(tempLoc)
							dist_from_center2.append(abs(helplist.o(j).distToRootCenter-centricdistance))
					}
					k = dist_from_center2.min_ind()
					node = (2*(k+1)-1)/(2*nseg)
					printf("Number of segments and the node: %f\n",nseg)
					printf("Number of node: %f\n",node)
					tempLoc = new Location(node)		
					createInput(syn, tempLoc.loc)
					createStim(stim, 0.5, rseed)
					syncon = new NetCon(list_of_presynapses.o(0), list_of_synapses.o(0), 0, 0, G)
					list_of_netcons.append(syncon)		//list_of_netcons = netcon.synlist(list_of_netcons)
					list_of_synLocations.append(tempLoc)
					/*
					printf("Centric synapse has been created %d um from soma (%g nS, %g ms, %g ms).\n",list_of_synLocations.o(0).distToRootCenter, 1000*G, TAU1, TAU2)
					printf("Dendritic diameter at the syn. location: %g um.", list_of_Locations.o(i).secRef.sec.diam(node))
					*/
		}
	}
}
	
create_synapses()

// shape plot to see synapses
objref s
s = new Shape()	
s.observe(actCell.all)	
s.exec_menu("Show Diam")
s.exec_menu("View = plot")
actCell.synDendLoc.secRef.sec s.point_mark(list_of_synapses.o(0),2)


//define ionic concentrations
cli0_cl_ion = cli0_cldifus 	 
clo0_cl_ion = clo0_cldifus

hco3i0_hco3_ion = 16
hco3o0_hco3_ion = 26

forall{
	hco3i = 16 hco3o = 26
	cli=5 clo=133.5
}

init()
proc display_par(){
printf("PREL: %f \n",PREL)
printf("Initial ECL: %f mV\n",ecl)
printf("EHCO3: %f mV\n",ehco3)
EGABA0 = PREL*ehco3+(1-PREL)*ecl
printf("Initial EGABA: %f mV\n",EGABA0)
}
display_par()


load_file("rig_single.ses")
load_file("plot_single.ses")







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