Effect of voltage sensitive fluorescent proteins on neuronal excitability (Akemann et al. 2009)

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Accession:123453
"Fluorescent protein voltage sensors are recombinant proteins that are designed as genetically encoded cellular probes of membrane potential using mechanisms of voltage-dependent modulation of fluorescence. Several such proteins, including VSFP2.3 and VSFP3.1, were recently reported with reliable function in mammalian cells. ... Expression of these proteins in cell membranes is accompanied by additional dynamic membrane capacitance, ... We used recordings of sensing currents and fluorescence responses of VSFP2.3 and of VSFP3.1 to derive kinetic models of the voltage-dependent signaling of these proteins. Using computational neuron simulations, we quantitatively investigated the perturbing effects of sensing capacitance on the input/output relationship in two central neuron models, a cerebellar Purkinje and a layer 5 pyramidal neuron. ... ". The Purkinje cell model is included in ModelDB.
Reference:
1 . Akemann W, Lundby A, Mutoh H, Knöpfel T (2009) Effect of voltage sensitive fluorescent proteins on neuronal excitability. Biophys J 96:3959-76 [PubMed]
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: Cerebellum;
Cell Type(s): Cerebellum Purkinje GABA cell;
Channel(s): I Na,t; I A; I K; I h; I K,Ca; I Calcium;
Gap Junctions:
Receptor(s):
Gene(s): Kv1.1 KCNA1; Kv4.3 KCND3; Kv3.3 KCNC3; Kv3.4 KCNC4; HCN1;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s):
Implementer(s): Akemann, Walther [akemann at brain.riken.jp];
Search NeuronDB for information about:  Cerebellum Purkinje GABA cell; I Na,t; I A; I K; I h; I K,Ca; I Calcium; 
/*~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
	Plot of VSFP responses in Fig. 9 A, 9B1, 9B2, 9C1, 9C2 
	of Akemann et al. Biophys. J. (2009) 96:3959-3976

	Laboratory for Neuronal Circuit Dynamics
	RIKEN Brain Science Institute, Wako City, Japan
	http://www.neurodynamics.brain.riken.jp

	Date of Implementation: July 2008
	Contact: akemann@brain.riken.jp
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~*/

load_file("morphology_mechanisms.hoc")
load_file("nrngui.hoc")

objref fig9A, fig9B1, fig9B2, fig9C1, fig9C2
objref vbox

begintemplate protocol
public stimStart, stimEnd, end, ampBase, ampStim, traceDT
stimStart = 0
stimEnd = 0
end = 0
ampBase = 0
ampStim = 0
traceDT = 0
endtemplate protocol


//*********************************************************************************
proc run_model() { localobj time, voltage, VP23activation, VP23fluorescence, VP31activation, VP31fluorescence, electrode 
// $o1 protocol

if( $o1.stimStart >= $o1.stimEnd || $o1.stimEnd >= $o1.end ) {
	print "Input error!"
	return }
 
time = new Vector()
voltage = new Vector()
VP23activation = new Vector()
VP23fluorescence = new Vector()
VP31activation = new Vector()
VP31fluorescence = new Vector()

soma electrode = new IClamp(0.5)

soma nc_VSFP23M3 = 0
soma nc_VSFP31M3 = 0

simulate( $o1, time, voltage, electrode )

soma nc_VSFP23M3 = 500e8	// 500 units per um2
soma nc_VSFP31M3 = 0

simulateVSFP23( $o1, VP23activation, VP23fluorescence, electrode )
if( stoprun == 1 ) return

soma nc_VSFP23M3 = 0
soma nc_VSFP31M3 = 500e8

simulateVSFP31( $o1, VP31activation, VP31fluorescence, electrode )
if( stoprun == 1 ) return

vbox=new VBox()
vbox.intercept(1)

  fig9A = new Graph()
  fig9A.size( 0, 10, -1, 1 )
  voltage.line( fig9A, time )
  fig9A.label("voltage")
  fig9A.exec_menu("View = plot")
  fig9A.label(0.15, 0.5, "fig9A")

  fig9B1 = new Graph()
  fig9B1.size( 0, 10, -1, 1 )
  VP23activation.line( fig9B1, time )
  fig9B1.label("VSFP23 activation")
  fig9B1.exec_menu("View = plot")
  fig9B1.label(0.15, 0.5, "fig9B1")

  fig9B2 = new Graph()
  fig9B2.size( 0, 10, -1, 1 )
  VP23fluorescence.line( fig9B2, time )
  fig9B2.label("VSFP23 fluorescence")
  fig9B2.exec_menu("View = plot")
  fig9B2.label(0.15, 0.5, "fig9B2")

  fig9C1 = new Graph()
  fig9C1.size( 0, 10, -1, 1 )
  VP31activation.line( fig9C1, time )
  fig9C1.label("VSFP31 activation")
  fig9C1.exec_menu("View = plot")
  fig9C1.label(0.15, 0.5, "fig9C1")

  fig9C2 = new Graph()
  fig9C2.size( 0, 10, -1, 1 )
  VP31fluorescence.line( fig9C2, time )
  fig9C2.label("VSFP31 fluorescence")
  fig9C2.exec_menu("View = plot")
  fig9C2.label(0.15, 0.5, "fig9C2")

vbox.intercept(0)
vbox.map("figure 9 left panel simulations Akemann et al. 2009",120,180,600,500)

}  
	
//**********************************************************************
proc simulate() { 
//	$o1 protocol
//	$o2 time vector
//	$o3 voltage vector
//	$o4 electrode

if($o1.traceDT > dt) {$o1.traceDT = int($o1.traceDT/dt) * dt} else {$o1.traceDT = dt}

$o2.resize(int($o1.end/$o1.traceDT)+1)
$o3.resize(int($o1.end/$o1.traceDT)+1)

$o2.record( &t, $o1.traceDT )
$o3.record( &soma.v(0.5), $o1.traceDT )

$o4.del = 0
$o4.dur = $o1.end
$o4.amp = $o1.ampBase

tstop = $o1.stimStart
run()
if( stoprun ==1 ) return

$o4.amp = $o1.ampStim
continuerun($o1.stimEnd)
if( stoprun == 1 ) return

$o4.amp = $o1.ampBase
continuerun($o1.end)
if ( stoprun == 1) return

}

//**********************************************************************
proc simulateVSFP23() { 
//	$o1 protocol
//	$o2 VPactivation vector
//	$o3 VPfluorescence vector
//	$o4 electrode


if($o1.traceDT > dt) {$o1.traceDT = int($o1.traceDT/dt) * dt} else {$o1.traceDT = dt}

$o2.resize(int($o1.end/$o1.traceDT)+1)
$o3.resize(int($o1.end/$o1.traceDT)+1)

$o2.record( &soma.fluoActivation_VSFP23M3(0.5), $o1.traceDT )
$o3.record( &soma.fluoSignal_VSFP23M3(0.5), $o1.traceDT )

$o4.del = 0
$o4.dur = $o1.end
$o4.amp = $o1.ampBase

tstop = $o1.stimStart
run()
if( stoprun ==1 ) return

$o4.amp = $o1.ampStim
continuerun($o1.stimEnd)
if( stoprun == 1 ) return

$o4.amp = $o1.ampBase
continuerun($o1.end)
if ( stoprun == 1) return

}

// ***************************************************************************
proc simulateVSFP31() { 
//	$o1 protocol
//	$o2 VPactivation vector
//	$o3 VPfluorescence vector
//	$o4 electrode


if($o1.traceDT > dt) {$o1.traceDT = int($o1.traceDT/dt) * dt} else {$o1.traceDT = dt}

$o2.resize(int($o1.end/$o1.traceDT)+1)
$o3.resize(int($o1.end/$o1.traceDT)+1)

$o2.record( &soma.fluoActivation_VSFP31M3(0.5), $o1.traceDT )
$o3.record( &soma.fluoSignal_VSFP31M3(0.5), $o1.traceDT )

$o4.del = 0
$o4.dur = $o1.end
$o4.amp = $o1.ampBase

tstop = $o1.stimStart
run()
if( stoprun ==1 ) return

$o4.amp = $o1.ampStim
continuerun($o1.stimEnd)
if( stoprun == 1 ) return

$o4.amp = $o1.ampBase
continuerun($o1.end)
if ( stoprun == 1) return

}


//************* Main *******************************************

objref prot
prot = new protocol()

prot.stimStart = 200
prot.stimEnd = 400
prot.end = 700
prot.ampBase = -0.020		// (nA)
prot.ampStim = 0		// (nA)

dt = 0.005
v_init = -69.7

nrnsecmenu(0.5, 1)
//if( ismembrane("VSFP23M3") ) nrnglobalmechmenu("VSFP23M3")
//if( ismembrane("VSFP31M3") ) nrnglobalmechmenu("VSFP31M3")

xpanel("Figure 9 left panel")

xvalue("Start stimulus (ms)", "prot.stimStart")
xvalue("End of Simulation (ms)", "prot.stimEnd")
xvalue("End of Protocol (ms)", "prot.end")
xlabel("")
xvalue("Baseline current (nA)", "prot.ampBase")
xvalue("Stimulus current (nA)", "prot.ampStim")

xlabel("")
xvalue("dt", "dt")
xvalue("t", "t")
xbutton("Stop", "stoprun = 1")
xlabel("")

xbutton("Start", "run_model( prot )")
xlabel("")
xpanel()

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