TITLE R-type calcium current (Cav2.3) COMMENT neuromodulation is added as functions: modulation = 1 + damod*(maxMod-1)*level where: damod [0]: is a switch for turning modulation on or off {1/0} maxMod [1]: is the maximum modulation for this specific channel (read from the param file) e.g. 10% increase would correspond to a factor of 1.1 (100% +10%) {0-inf} level [0]: is an additional parameter for scaling modulation. Can be used simulate non static modulation by gradually changing the value from 0 to 1 {0-1} [] == default values {} == ranges ENDCOMMENT UNITS { (mV) = (millivolt) (mA) = (milliamp) (S) = (siemens) (molar) = (1/liter) (mM) = (millimolar) FARADAY = (faraday) (coulomb) R = (k-mole) (joule/degC) } NEURON { SUFFIX car USEION ca READ cai, cao WRITE ica VALENCE 2 RANGE pbar, ica RANGE damod, maxMod, level, max2, lev2 } PARAMETER { pbar = 0.0 (cm/s) :q = 1 : room temperature 22 C q = 3 : body temperature 35 C damod = 0 maxMod = 1 level = 0 max2 = 1 lev2 = 0 } ASSIGNED { v (mV) ica (mA/cm2) eca (mV) celsius (degC) cai (mM) cao (mM) minf mtau (ms) hinf htau (ms) } STATE { m h } BREAKPOINT { SOLVE states METHOD cnexp ica = pbar*m*m*m*h*ghk(v, cai, cao) *modulation() } INITIAL { rates() m = minf h = hinf } DERIVATIVE states { rates() m' = (minf-m)/mtau*q h' = (hinf-h)/htau*q } PROCEDURE rates() { UNITSOFF minf = 1/(1+exp((v-(-29))/(-9.6))) mtau = 5.1*3 hinf = 1/(1+exp((v-(-33.3))/17)) htau = 22+80/(1+exp((v-(-19))/5)) UNITSON } FUNCTION ghk(v (mV), ci (mM), co (mM)) (.001 coul/cm3) { LOCAL z, eci, eco z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15)) if(z == 0) { z = z+1e-6 } eco = co*(z)/(exp(z)-1) eci = ci*(-z)/(exp(-z)-1) ghk = (1e-3)*2*FARADAY*(eci-eco) } FUNCTION modulation() { : returns modulation factor modulation = 1 + damod * ( (maxMod-1)*level + (max2-1)*lev2 ) if (modulation < 0) { modulation = 0 } } COMMENT Original data by Foehring et al (2000) [1] for dissociated MSNs from P28-P42 Sprague-Dawley rat brain. Unspecified recording temperature. The liquid junction potential was around 8 mV and was not corrected. Kinetics of m3h type was fitted. Inactivation time constants were measured in neurons from endopiriform nucleus of P7-P21 Hartley guinea pigs [2] at room temperature 22 C. Original NEURON model by Wolf (2005) [3] modified by Alexander Kozlov . Activation curve fitted to m3 kinetics [4], activation time constant scaled up as well. Smooth fit of inactivation time constant from [2,3]. [1] Foehring RC, Mermelstein PG, Song WJ, Ulrich S, Surmeier DJ (2000) Unique properties of R-type calcium currents in neocortical and neostriatal neurons. J Neurophysiol 84(5):2225-36. [2] Brevi S, de Curtis M, Magistretti J (2001) Pharmacological and biophysical characterization of voltage-gated calcium currents in the endopiriform nucleus of the guinea pig. J Neurophysiol 85(5):2076-87. [3] Wolf JA, Moyer JT, Lazarewicz MT, Contreras D, Benoit-Marand M, O'Donnell P, Finkel LH (2005) NMDA/AMPA ratio impacts state transitions and entrainment to oscillations in a computational model of the nucleus accumbens medium spiny projection neuron. J Neurosci 25(40):9080-95. [4] Evans RC, Maniar YM, Blackwell KT (2013) Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates. J Neurophysiol 110(7):1631-45. ENDCOMMENT