TITLE LVA L-type calcium current (Cav1.3) 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 { THREADSAFE SUFFIX cal13 USEION cal READ cali, calo WRITE ical VALENCE 2 RANGE pbar, ical RANGE damod, maxMod, level, max2, lev2 } PARAMETER { pbar = 0.0 (cm/s) :q = 1 : room temperature 22-25 C q = 2 : body temperature 35 C damod = 0 maxMod = 1 level = 0 max2 = 1 lev2 = 0 } ASSIGNED { v (mV) ical (mA/cm2) ecal (mV) celsius (degC) cali (mM) calo (mM) minf mtau (ms) hinf htau (ms) } STATE { m h } BREAKPOINT { SOLVE states METHOD cnexp ical = pbar*m*m*h*ghk(v, cali, calo) *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-(-33))/(-6.7))) :mtau = 0.06+1/(0.06*exp((v-(-46))/20)+0.41*exp((v-26)/-48)) mtau = 0.06+1/(exp((v-10)/20)+exp((v-(-17))/-48)) hinf = 1/(1+exp((v-(-13.4))/11.9)) htau = 44.3 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 Activation curve was reconstructed for cultured NAc neurons from P5-P32 Charles River rat pups [1] and shifted to match LVA data [7, Fig.1D]. Activation time constant is from the rodent neuron culture (both rat and mouse cells), room temperature 22-25 C [2, Fig.15A]. Inactivation curve of CaL v1.3 current was taken from HEK cells [3, Fig.2 and p.819] at room temperature. Original NEURON model by Wolf (2005) [4] was modified by Alexander Kozlov . Kinetics of m2h type was used [5,6]. Activation time constant was refitted to avoid singularity. [1] Churchill D, Macvicar BA (1998) Biophysical and pharmacological characterization of voltage-dependent Ca2+ channels in neurons isolated from rat nucleus accumbens. J Neurophysiol 79(2):635-47. [2] Kasai H, Neher E (1992) Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a mammalian neuroblastoma-glioma cell line. J Physiol 448:161-88. [3] Bell DC, Butcher AJ, Berrow NS, Page KM, Brust PF, Nesterova A, Stauderman KA, Seabrook GR, Nurnberg B, Dolphin AC (2001) Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. J Neurophysiol 85:816-827. [4] 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. [5] Evans RC, Morera-Herreras T, Cui Y, Du K, Sheehan T, Kotaleski JH, Venance L, Blackwell KT (2012) The effects of NMDA subunit composition on calcium influx and spike timing-dependent plasticity in striatal medium spiny neurons. PLoS Comput Biol 8(4):e1002493. [6] Tuckwell HC (2012) Quantitative aspects of L-type Ca2+ currents. Prog Neurobiol 96(1):1-31. [7] Xu W, Lipscombe D (2001) Neuronal cav1.3 L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J Neurosci 21(16): 5944-5951. ENDCOMMENT