Molecular layer interneurons in cerebellum encode valence in associative learning (Ma et al 2020)

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Accession:266578
We used two-photon microscopy to study the role of ensembles of cerebellar molecular layer interneurons (MLIs) in a go-no go task where mice obtain a sugar water reward. In order to begin understanding the circuit basis of our findings in changes in lick behavior with chemogenetics in the go-no go associative learning olfactory discrimination task we generated a simple computational model of MLI interaction with PCs.
Reference:
1 . Ma M, Futia GL, De Souza FM, Ozbay BN, Llano I, Gibson EA, Restrepo D (2020) Molecular layer interneurons in the cerebellum encode for valence in associative learning Nature Communications, accepted
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; Mouse;
Cell Type(s): Cerebellum Purkinje GABA cell; Cerebellum interneuron stellate GABA cell;
Channel(s):
Gap Junctions:
Receptor(s): AMPA; GabaA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Action Potentials; Detailed Neuronal Models;
Implementer(s): Simoes-de-Souza, Fabio [fabio.souza at ufabc.edu.br];
Search NeuronDB for information about:  Cerebellum Purkinje GABA cell; Cerebellum interneuron stellate GABA cell; GabaA; AMPA; Gaba; Glutamate;
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MaEtAl2020
README.html
bkpkj.mod *
cad.mod *
cadiff.mod *
cae.mod *
cap2.mod *
captain.mod *
cat.mod *
cha.mod *
erg.mod *
gkca.mod *
Golgi_Ca_LVA.mod *
Golgi_KA.mod *
Golgi_KV.mod
Golgi_Na.mod *
hpkj.mod *
k23.mod *
ka.mod *
kc3.mod *
kd.mod *
kdyn.mod *
khh.mod *
km.mod *
kpkj.mod *
kpkj2.mod *
kpkjslow.mod *
kv1.mod *
leak.mod *
lkpkj.mod *
myexchanger.mod *
myexchangersoma.mod *
mypump.mod *
mypumpsoma.mod *
nadifl.mod *
narsg.mod *
newnew.mod *
pump.mod *
10480.tmp
2_compartment_template.hoc
full.ses *
lesbos.ses *
mosinit.hoc
mosinit_PC_SC_SminusCNO.hoc
mosinit_PC_SC_SminusSaline.hoc
mosinit_PC_SC_SplusCNO.hoc
mosinit_PC_SC_SplusSaline.hoc
PC_alx.swc
PF_template.hoc
Plot_results.m
SC_morphology.hoc
SC_template.hoc
SC_withoutaxon.swc
screenshot.png
                            
//load_file("nrngui.hoc")

begintemplate Purkinje_simple

public soma, Couple, nclist
public x, y, z
public Esynapse, Isynapse_dist, Isynapse_prox, Isynapse_BG

//counting spikes
public spiketimes,spikecount
objref spiketimes,spikecount

public voltagem
objref voltagem

public position

alcohol = 0        // IF THIS IS SET TO 1 THEN WE IMPLEMENT THE ALCOHOL PUMP DECLINE 
// Note that for alcohol experiments you need to set km of pump.mod to be 12 instead of 40
multiple = 1           // this is a single parameter that can affect the rate of decline. But is more complicated than this though, so take a look at code below. 


create soma
create Couple

objectvar nclist
objectvar Esynapse, Isynapse_dist, Isynapse_prox, Isynapse_BG

proc init() {
x=$1
y=$2
z=$3


create soma
nclist=new List()

spiketimes=new Vector()
lastspikecount=0

voltagem=new Vector()


soma	      {
pt3dclear()
pt3dadd(x,y,z,50)
pt3dadd(x+50,y,z,50) 	
nseg=1 L=22 diam=22 
}

length = 529.29

diamax = 4311.37/(3.14*length)
diamax_2 = sqrt(diamax)
diamax_3 = diamax_2 * 2

Couple {
nseg=1 L= length diam= diamax_3 
Esynapse = new Exp2Syn(0.5)      //AMPAR
Esynapse.tau1=0.28 //ms rise time (Hausser and Roth, 1997)
Esynapse.tau2=1.23  //ms decay time (Hausser and Roth, 1997)
Esynapse.e=0       //mV reversal potential

Isynapse_prox = new Exp2Syn(0.5)      //GABAaR 
Isynapse_prox.tau1=1.8 //ms rise time 
Isynapse_prox.tau2=8.5  //ms decay time
Isynapse_prox.e=-85       //mV reversal potential (Houston, 2009)

Isynapse_dist = new Exp2Syn(1.0)      //GABAaR 
Isynapse_dist.tau1=1.8 //ms rise time
Isynapse_dist.tau2=8.5  //ms decay time
Isynapse_dist.e=-85       //mV reversal potential (Houston, 2009)

Isynapse_BG = new Exp2Syn(0.75)      //GABAaR 
Isynapse_BG.tau1=1.8 //ms rise time (references ?) 
Isynapse_BG.tau2=8.5  //ms decay time (references ?)
Isynapse_BG.e=-85       //mV reversal potential (Houston, 2009)


}  

access soma
 soma connect Couple(0),1

// length = 529.29, DIAMETER = 3.22
// DO NOT GET CONFUSEd WITH RADIUS AND DIAMETER

a=0 
forall for (x) a += area(x) 

corrD = 42310/a 


// global_ra = 250
// set_ra()


access soma
soma {

cm = 0.8

insert narsg      // Na current. Resurgent. Markov model
insert hpkj       // Ih              hyperpolarisation activated cation current
insert bkpkj      // BK ca2+ dependent K+ current
insert cadiff     // calcium diffusion
insert kpkj
insert kpkj2
insert kpkjslow
insert captain        // P type ca. P type calcium current

gbar_narsg = 0.156     
ghbar_hpkj = 0.00104           
gkbar_bkpkj = 0.0728
gkbar_kpkj = 0.0416        
gkbar_kpkj2 = 0.0208       
gkbar_kpkjslow = 0.0416     
pcabar_captain = 0.00052   //  0.00005 

insert lkpkj      // leak current
e_lkpkj = -70
g_lkpkj = 0.0001

ena = 60
ek = -88

// -------------------
insert pump 
km_pump = 40                 // Michaelis-Menten
n_pump = 1
decline_pump = alcohol        // If this is set to 1 then we switch on the oubain/alcohol pump decline system
initialdensity_pump = 1   // this is the density before the decline or the fixed density if no decline is chosen
red_pump = 0           // this is the lag before the decline takes place
lex_pump = 70 * multiple                    // this sets the speed of the decline
// -------------------

insert nadifl D_nadifl = 0.60 
tau_nadifl = 5000  

insert myexchangersoma

//----------------------
insert mypumpsoma
decline_mypumpsoma = alcohol                       // If this is set to 1 then we switch on the oubain/alcohol pump decline system
initialdensity_mypumpsoma = 0.5             // this is the density before the decline or the fixed density if no decline is chosen
red_mypumpsoma = 50000           // this is the lag before the decline takes place
lex_mypumpsoma = 200 * multiple                   // this sets the speed of the decline
green_mypumpsoma = 50000           // this is the lag before the second rate of decline takes place
lux_mypumpsoma = 200 * multiple                    // this sets the speed of the second set of decline
//----------------------

insert gkca
gkbar_gkca = 0.01

}




Couple   {

cm=0.8 * corrD 

insert cha   gkhbar_cha = 0.00028914405 * corrD       // Ih              hyperpolarisation activated cation current. CHANGED NAME
 
insert leak 
gl_leak = (7.93319415*10^-5) * corrD
el_leak = -80
 
nab = 0.036    //  KD
ruti = 0.032   // KA
tt =  0.001    // Whalter Kv1.1 (or maybe kv1.2)

        insert cap2 cai = 4e-5 cao = 2.4 gcabar_cap2 = 0.0016 * corrD
         insert cat cai = 4e-5 cao = 2.4  gcabar_cat = 0.0006 * corrD
         insert cae cai = 4e-5 cao = 2.4  gcabar_cae = 0.0032 * corrD
         insert khh gkbar_khh = 0.00024 * corrD
         insert km  gkbar_km  = 0.000004 * corrD
         insert ka  gkbar_ka  = ruti * corrD
         insert kd  gkbar_kd  = nab * corrD
         insert kc3 gkbar_kc3  = 0.06 * corrD
         insert k23 gkbar_k23  = 0.000156 * corrD
         insert cad taur_cad = 2 cainf_cad = 4e-5
		    kt_cad = 4e-5 kd_cad = 4e-5 
depth_cad = 0.1  * corrD

insert kv1
gbar_kv1 = tt * corrD

insert kdyn
KAF_kdyn = 0.0119 // bursts at 5,149 
// 0.01 - no bursts // 0.012 - bursts at 5000  // 0.013 bursts at around 3,500 // 0.015 bursts at around 2,500 // 0.02 - bursts at around 1000  
// OLD: 0.1428571428571  //  0.008  // 0.011    //  (~50:50)
// OLD: IN FULL MODEL IS 0.143, IN 40 COMPARTMENT IS 0.033, IN 5 COMPARTMENT IS 0.02. IN 2 COMPARTMENT IS 0.008 (BUT if Ra = 250+length = 240, it is 0.0055)
dep_kdyn = 70e-3    // Have not applied corrD to the depth
peak_kdyn = 3.03     // peak value of extracellular K concentration (because of buffering system)

insert myexchanger
ImaxNax_myexchanger = 0.00208768267 * corrD


//----------------------

insert mypump
decline_mypump = alcohol                                 // If this is set to 1 then we switch on the oubain/alcohol pump decline system
initialdensity_mypump = 0.00208768267 * corrD              // this is the density before the decline or the fixed density if no decline is chosen
red_mypump = 50000                                         // this is the lag before the decline takes place
lex_mypump = 200 * multiple                                            // this sets the speed of the decline

//----------------------
insert newnew
km_newnew = 2.245        
n_newnew = 1
decline_newnew = alcohol                                   // If this is set to 1 then we switch on the oubain/alcohol pump decline system
initialdensity_newnew = 0.0010438413 * corrD         // this is the density before the decline or the fixed density if no decline is chosen
red_newnew = 50000           // this is the lag before the decline takes place
lex_newnew = 200 * multiple                   // this sets the speed of the decline
//----------------------

// YOUR OWN ERG CURRENT (sequential, Hodgkin-Huxley)
insert erg
gbar_erg = 0 * corrD     //  0.01, 0.03 too small    0.1 does it, 0.05 does it.     (with vhalf = -5)
vhalf_erg = -5   // - 35 is the default, but you could legitimately change this to -5 because it is -5 with physiological levels of external calcium 
// (external calcium allosterically effects the channel)

//counting spikes
spikecount=new APCount(0.5)
spikecount.thresh=-20
spikecount.record(spiketimes)

//Saving Vm
voltagem.record(&v(0.5))

}
}

//Fabio´s stuff
proc position() {local i
  access soma 
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
}


endtemplate Purkinje_simple

// ------------------------------------
// Some global stuff. 
// ------------------------------------


celsius = 36
v_init=-65

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