NMDA receptor saturation (Chen et al 2001)

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Accession:7988
Experiments and modeling reported in the paper Chen N, Ren J, Raymond LA, and Murphy T (2001) support the hypothesis that glutamate has a relatively lower potency at NMDARs than previously thought from agonist application under equilibrium conditions. Further information and reprint requests are available from Dr T.H. Murphy thmurphy at interchange.ubc.ca
Reference:
1 . Chen N, Ren J, Raymond LA, Murphy TH (2001) Changes in agonist concentration dependence that are a function of duration of exposure suggest N-methyl-D-aspartate receptor nonsaturation during synaptic stimulation. Mol Pharmacol 59:212-9 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s):
Gap Junctions:
Receptor(s): NMDA;
Gene(s): NR2A GRIN2A; NR2B GRIN2B;
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Ion Channel Kinetics;
Implementer(s): Murphy, Tim H [THMurphy at interchange.ubc.ca];
Search NeuronDB for information about:  NMDA; Glutamate;
/*----------------------------------------------------------------------------

	Detailed kinetic synapse mechanism
	----------------------------------

	Demo file to show the behavior of a synaptic currents mediated by
	glutamate NMDA receptors, using a detailed kinetic model of these
	receptors and a kinetic model for the release of transmitter.

	Kinetic model from Clements & Westbrook, Neuron 7: 605, 1991.


  See details in:

  Destexhe, A., Mainen, Z.F. and Sejnowski, T.J.  Kinetic models of 
  synaptic transmission.  In: Methods in Neuronal Modeling (2nd edition; 
  edited by Koch, C. and Segev, I.), MIT press, Cambridge, 1996.


  Written by Alain Destexhe, Laval University, 1995

----------------------------------------------------------------------------*/



//----------------------------------------------------------------------------
//  load and define general graphical procedures
//----------------------------------------------------------------------------

xopen("$(NEURONHOME)/lib/hoc/stdrun.hoc")

objectvar g[20]			// max 20 graphs
ngraph = 0

proc addgraph() { local ii	// define subroutine to add a new graph
				// addgraph("variable", minvalue, maxvalue)
	ngraph = ngraph+1
	ii = ngraph-1
	g[ii] = new Graph()
	g[ii].size(0,tstop,$2,$3)
	g[ii].xaxis()
	g[ii].yaxis()
	g[ii].addvar($s1,1,0)
	g[ii].save_name("graphList[0].")
	graphList[0].append(g[ii])
}

if(ismenu==0) {
  nrnmainmenu()			// create main menu
//  nrncontrolmenu()		// create control menu
  ismenu=1
}






//----------------------------------------------------------------------------
//  create compartments and insert passive properties
//----------------------------------------------------------------------------

create PRE,POST
forall {
  diam=10
  L=10
  insert pas
  g_pas=1/5000
  e_pas=v_init
}



//----------------------------------------------------------------------------
//  insert presynaptic mechanisms
//----------------------------------------------------------------------------

access PRE		// insert Hodgk-Hux. Na+ and K+ currents for spikes


insert relramp		// transmitter release



//----------------------------------------------------------------------------
//  insert postsynaptic mechansisms
//----------------------------------------------------------------------------

objectvar c
c = new IVNMDA5()			// create synapse
POST c.loc(0.5)				// assign postsynaptic compartment
setpointer c.C, PRE.T_relramp(0.5)		// assign presynaptic compartment

Erev_IVNMDA5	= 0	//	(mV)	reversal potential (E_K)
mg_IVNMDA5	= 0	//	put in zero magnesium for the demo

// parameters from Hessler Shirke & Malinow 1993
Rb_IVNMDA5	= 0.02    //	(/uM /ms)	: binding 		
Ru_IVNMDA5	= 0.1  //	(/ms)	: unbinding		
Rd_IVNMDA5	= 0.004   //	(/ms)	: desensitization
Rr_IVNMDA5	= 0.0064   //	(/ms)	: resensitization 
Ro_IVNMDA5	= 0.32   //	(/ms)	: opening
Rc_IVNMDA5	= 0.32  //	(/ms)	: closing
c.gmax 	= 50	//	(pS)	maximum conductance




//----------------------------------------------------------------------------
//  add graphs
//----------------------------------------------------------------------------

//	addgraph("PRE.v(0.5)",-90,40)
//	addgraph("PRE.T_relramp(0.5)",0,1.5)
//	addgraph("c.inmda",-0.001, 0.0001)
//	addgraph("POST.v(0.5)",v_init-2,v_init+4)


//----------------------------------------------------------------------------
//  general parameters
//----------------------------------------------------------------------------

//iterator case() {local j
//		for j = $2, numarg()-1 {
//			$&1 = $j
//			iterator_statement
//		}
//}

double con[13]
con[0] = 0.00003
con[1] = 0.0001
con[2] = 0.0003
con[3] = 0.001
con[4] = 0.003
con[5] = 0.01
con[6] = 0.03
con[7] = 0.1
con[8] = 0.3
con[9] = 1
con[10] = 3
con[11] = 10
con[12] = 30

double duration[3]
duration[0] = 1
duration[1] = 20
duration[2] = 2000

double ramp[3]
ramp[0] = 0.2
ramp[1] = 4
ramp[2] = 4

count = 0
double x[3101/0.025]
for jj = 0,2 {

	dt = 0.025
	ttstop = duration[jj] + 100
	tstop = ttstop

	runStopAt = ttstop
	steps_per_ms = 1/dt
	celsius = 36
	v_init = -70

	
	for mm = 0,12 {
		
		c.gluc = con[mm]
		c.w = 0
		c.timer = ttstop
		c.llabel = 0.0

		access PRE
		cmax_relramp = con[mm]
		dur_relramp = duration[jj]
		rampdur_relramp = ramp[jj]
		
		
		finitialize()
		wopen("current.dat")
		
		
		while( t < tstop) {
			fadvance()
			
       		fprint("%e \n", c.inmda)
       	      
		      if (c.llabel == 3.0) {
				
				wopen()
				ropen("current.dat")
				for (j = 0; j < t/dt; j = j +1) {
					x[j] = 0.0
				}
				for (j=1; j<t/dt; j=j+1) {
	
			          x[j] = fscan()
				    temp1 = 0.1 * c.inmda
				    temp2 = 0.9 * c.inmda
				    if((x[j]*1e10 <= temp1*1e10)&&(x[j-1]*1e10 >= temp1*1e10)) {
						time10 = j*dt
				    }
				    if((x[j]*1e10 <= temp2*1e10)&&(x[j-1]*1e10 > temp2*1e10)) {
						time90 = j*dt
						print  time10, time90,x[j],temp2
				    		break
					}
				    
				}
			      ropen()
				risetime = time90 - time10
				print cmax_relramp
				print risetime

				break
			}

		}
	}
}
	



			
	
	

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