ModelDB: Spiny neuron model with dopamine-induced bistability (Gruber et al 2003)

SenseLab Home ModelDB Home

Spiny neuron model with dopamine-induced bistability (Gruber et al 2003)
Accession: 39949
These files implement a model of dopaminergic modulation of voltage-gated currents (called kir2 and caL in the original paper). See spinycell.html for details of usage and implementation. For questions about this implementation, contact Ted Carnevale (ted.carnevale@yale.edu)
Reference: Gruber AJ, Solla SA, Surmeier DJ, Houk JC (2003) Modulation of striatal single units by expected reward: a spiny neuron model displaying dopamine-induced bistability. J Neurophysiol 90:1095-114 [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;
Brain Region(s)/Organism:  
Cell Type(s):  Neostriatum spiny direct pathway neuron;  
Channel(s):  I K,leak; I h; I A, slow;  
Gap Junctions:  
Receptor(s):  D1; Dopaminergic Receptor;
Gene(s):  Cav1.3 CACNA1D; D1 DRD1A;
Transmitter(s):  Dopamine;
Simulation Environment:  NEURON;
Model Concept(s):  Synaptic modulation of active currents;
Implementer(s):  Carnevale, Ted [Ted.Carnevale at Yale.edu];
Search NeuronDB for information about:  Neostriatum spiny direct pathway neuron; D1; Dopaminergic Receptor; I K,leak; I h; I A, slow; Dopamine;
\
spinycell
figs
readme.html
damsg.mod
gspike.mod
kir2.mod
ksi.mod
leak.mod
caL.mod
fig10network.hoc
fig10syn.hoc
fig3BC.hoc
fig4.hoc
fig6.hoc
fig7a.hoc
fig7acontrol.hoc
fig7b.hoc
fig7bcontrol.hoc
fig7syn.hoc
figs2and3A.hoc
c_cell.hoc
exptl_conditions.hoc
fig10ab.hoc
mosinit.hoc
fig6netrig.ses
fig10netrig.ses
figs2and3A.ses
fig10netcells.ses
damsgtest.ses
fig6net.ses
fig6netcells.ses
model_mu_1.ses
fig7rig.ses
fig10net.ses
                            
NEURON implementation of spiny neuron model

NEURON implementation of spiny neuron model

These programs reproduce figures from the paper
"Modulation of Striatal Single Units by Expected Reward: A Spiny Neuron Model Displaying Dopamine-Induced Bistability"
Aaron J. Gruber, Sara A. Solla, D., James Surmeier, and James C. Houk
J Neurophysiol 90: 1095 1114, 2003

Address questions to Ted Carnevale
ted.carnevale@yale.edu

The following comments show how to operate these programs, and discuss the implementation of the models and how to reuse this code.


Usage

  1. Unzip spinycell.zip into an empty directory.
  2. Compile the mod files with nrnivmodl (or mknrndll if you're using MSWin)
  3. Follow the instructions below.


Figs. 2 and 3A

Use NEURON to execute figs2and3A.hoc
Click on the Plot button in each of the three Graphers.


Figs. 3B and C

Use NEURON to execute fig3BC.hoc
Click one of the buttons in this small panel

to bring up a plot that reproduces Fig. 3B

or Fig. 3C


Fig. 4

Use NEURON to execute fig4.hoc
The graph is created automatically.


Fig. 6

Use NEURON to execute fig6.hoc
On the right there is a graph window. Just below this is a small panel with buttons labeled "Fig. 6a" and "Fig. 6b". Click on one of these to generate the corresponding family of plots.
Fig. 6a
Fig. 6b
Notes:
  1. The first 200-300 ms of each trace is a "warmup" or "stabilization" interval during which the model reaches a dynamic equilibrium appropriate for the baseline synaptic drive.
  2. The increase of synaptic drive starts at 400 ms.
  3. The pseudorandom afferent spike trains are different on each run, so each press of these buttons produces a slighly different family of traces. However, the envelopes of the individual trajectories are essentially similar from run to run.
    Example: repeat "Fig. 6b run"
  4. Mean synaptic conductance appears to be the primary determinant of the membrane potential trajectories. Other details of synaptic input (negexp ISI spike trains driving the relatively simple ExpSyn mechanism here, vs. the more complex, empirically derived model of synaptic activity used by Gruber et al.) affect only the low-level fluctuations of the individual traces.


Figs. 7A and B

Use NEURON to execute fig7a.hoc or fig7b.hoc
The graphs are created automatically.
Fig. 7A
Fig. 7B
Note: The actual values of mu used for the figures in the paper were not available. The values used in these programs are sufficient to demonstrate the same dynamical features of the model that were illustrated by the original figures.


Fig. 10A and B

Use NEURON to execute fig10ab.hoc
This brings up several windows, the rightmost of which are a stack of graphs. From the top down, these graphs will show
  • the membrane potential of the spiny neuron
  • the cortical input spike train
  • the time course of the modulatory action of dopaminergic input
Above these graphs is a small panel with four radio buttons that set the "experimental conditions." Select one of the four possible combinations and click on the RunControl's Init & Run button to launch a simulation.
Example 1: weak cortical input, target unrewarded

Example 2: strong cortical input, target rewarded

Notes:
  1. During the first few hundred ms, the model reaches a dynamic equilibrium appropriate for the background synaptic drive.
  2. Sequential runs under the same conditions will differ because a different afferent spike train is used each time.


Model implementation

Among these files there are actually two different implementations of a spiny neuron model. The first is used to generate the figures that illustrate the basic properties of the model (Figs. 2 - 4 and 7), and the second is used for those figures that show how dopamine affects the model's response to afferent spike trains (Figs. 6 and 10).

Both implementations use the same membrane currents, which are specified by these files:

  caL.mod
  kir2.mod
  ksi.mod
  leak.mod
Of these, only caL.mod includes temperature dependence (needs celsius = 20 to reproduce the figures from the paper).

Some of the programs also use the mechanisms specified in one or both of these files:

  damsg.mod
  gspike.mod
These mechanisms are described later in this document.


Implementation 1: a "stand-alone" model cell

The properties of the model used for Figs. 2 - 4 and 7 are specified by these graphical tools

These were set up with NEURON's GUI, and they are recreated by having NEURON execute the code in model_mu_1.ses. Think of this file as a "virtual experimental preparation," somewhat analogous to a single cell in tissue culture or an acutely isolated soma.

This file is loaded by the following programs :

  figs2and3A.hoc
  fig3BC.hoc
  fig4.hoc
  fig7a.hoc
  fig7b.hoc
It needs only one thing to be a complete specification of a model of a spiny neuron : some way for the caL and kir2 mechanisms to discover the value of the "dopamine message." In figs2and3A.hoc this is done by the statements
msg = 1

soma for (x,0) { // skip the nodes at 0 and 1
        setpointer mu_caL(x), msg
        setpointer mu_kir2(x), msg
}
which link the "mu" POINTERs of caL and kir2 to the hoc scalar msg. Except for fig7a.hoc and fig7b.hoc, the other programs that use model_mu_1.ses contain similar statements. This is OK for simulations in which mu remains constant or changes abruptly from one steady level to another.

For fig7a.hoc and fig7b.hoc, computational efficiency requires a different approach. Unlike other simulations involving the "stand-alone model," these need msg to have nontrivial dynamics. Using a hoc scalar and modifying NEURON's main computational loop to force incremental changes in msg at every fadvance() is not the best way to do this.

Therefore fig7a.hoc and fig7b.hoc employ a DAsyn point process. This "net-ready" synaptic mechanism has a state variable msg which, in this implementation, has first order dynamics and can be driven by spike events. The file fig7syn.hoc contains the statements that link the "mu" POINTERS of caL and kir2 to this msg.

DAsyn is also used in the program that reproduces Fig. 10 (see below).


Implementation 2: a "networked" model cell

The "networked" model cell is used by these two programs:
  fig6.hoc
  fig10ab.hoc
This model implementation has a "fast conductance change excitatory synapse" (ExpSyn) that receives spike trains representing afferent cortical activity. It happens to be implemented with NEURON's NetReadyCellGUI tool, but its anatomical and biophysical properties are identical to those of the "stand-alone" model.

The NetReadyCellGUI tool that specifies the properties of this "biological model cell", and the ArtCellGUI tool that specifies the properties of the artificial spiking cells that generate the afferent spike trains, were created using NEURON's GUI and saved to session files called fig6netcells.ses and fig10netcells.ses.

As noted above, the conductance fluctuations used in the simulations reported by Gruber et al. are quite different from those generated by spike trains with negexp statistics converging on an ExpSyn mechanism. Even so, the simulation results produced by these files are qualitatively quite similar to the published figures. Mean synaptic conductance, rather than its detailed fluctuations, appears to be the principal factor that governs the time course of membrane potential.
Network architectures were specified with the NetGUI tool and saved to session files called fig6net.ses and fig10net.ses. "Instrumentation" (simulation controls and graphical displays of results) are contained in fig6netrig.ses and fig10netrig.ses.

fig6.hoc uses a simple hoc scalar called msg to represent dopaminergic effect, and the mu POINTERs of the caL and kir2 mechanisms are linked to it in the file fig6.hoc. As noted previously, the simulations that generate Figure 10 use a DAsyn point process so that msg can have its own dynamics and yet be computationally efficient. fig10syn.hoc contains the statements that link the mu POINTERs of caL and kir2 to the DAsyn's msg.

The "spike" mechanism used by Gruber et al. 2003 for Fig. 10 requires an implementation that demands fig10ab.hoc be run only with fixed time step integration (see gspike.mod).

Reusable hoc code

c_cell.hoc contains a template (class definition) for model neurons with properties identical to the one that was used to generate Fig. 10, complete with both an ExpSyn (to receive "cortical input spikes") and a DAsyn (to receive "dopaminergic input spikes"). It can be used, with or without NEURON's GUI, to spawn new instances of this model neuron that are suitable for use in network simulations.

load_file("c_cell.hoc")
objref foo
foo = new List()
for i=0,99 foo.append(new C_Cell())
foo.count()  // returns 100
// now there are 100 of these cells ready to be connected into a network
Caveat: Be sure to specify the operating temperature, e.g.
  celsius = 20
How I created c_cell.hoc
  1. Clicked on the "Hoc File" button of fig10ab.hoc's NetGUI tool and specified fig10network.hoc as the name of the output file
  2. Extracted the template for the C_Cell class from fig10network.hoc
  3. Finally, made one small but important modification to the C_Cell template:
    adding a "forsec all" loop to proc synapses() so that the mu POINTERs of every instance of caL and kir2 will be linked to the DAsyn's msg variable
Here's the modified proc synapses()--
proc synapses() {
  /* ExpSyn0 */   soma syn_ = new ExpSyn(0.5)  synlist.append(syn_)
    syn_.tau = 3
  /* DAsyn1 */   soma syn_ = new DAsyn(0.5)  synlist.append(syn_)
  // attach all POINTERs to DAsyn.msg
  forsec all {
    if (issection("caL")) {
      for (x,0) { // skip the nodes at 0 and 1
	setpointer mu_caL(x), synlist.object(1).msg
      }
    }
    if (issection("kir2")) {
      for (x,0) { // skip the nodes at 0 and 1
	setpointer mu_kir2(x), synlist.object(1).msg
      }
    }
  }
}
 
@SenseLabProject
ModelDB rss feeder          

ModelDB Home  SenseLab Home  Help
Questions, comments, problems? Email the ModelDB Administrator
How to cite ModelDB
This site is Copyright 2014 Shepherd Lab, Yale University

          Neuroinformatics at NIH           NIF