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Article contents:== Outdated egg! This is an egg for CHICKEN 4, the unsupported old release. You're almost certainly looking for [[/eggref/5/nemo|the CHICKEN 5 version of this egg]], if it exists. If it does not exist, there may be equivalent functionality provided by another egg; have a look at the [[https://wiki.call-cc.org/chicken-projects/egg-index-5.html|egg index]]. Otherwise, please consider porting this egg to the current version of CHICKEN. [[tags:egg]] == nemo An implementation of a description language for computational models of ion channels. [[toc:]] == Usage nemo [options...] [input files ...] == Documentation {{NEMO}} is a program that reads an ion channel description and generates corresponding model simulation code in [[http://www.gnu.org/software/octave/|GNU Octave]], [[http://www.nest-initiative.org/|NEST]] C++ code, or the [[http://www.neuron.yale.edu/neuron/docs/help/neuron/nmodl/nmodl.html|NMODL]] language used by the [[http://www.neuron.yale.edu/neuron/|NEURON simulator]]. === Options ; {{-i FORMAT}} : specify input format (nemo, xml, sxml, s-exp) ; {{-p}} : generate individual files for each current component in the input file ; {{--xml[=FILE]}} : write XML output to file (default: <model-name>.xml) ; {{--sxml[=FILE]}} : write SXML output to file (default: <model-name>.sxml) ; {{--nest}} : write NEST output to files <model-name>.cpp and <model-name>.h ; {{--nmodl[=FILE]}} : write NMODL output to file (default: <model-name>.mod) ; {{--nmodl-method=METHOD}} : specify NMODL integration method (cnexp, derivimplicit, cvode) ; {{--nmodl-kinetic=[STATES]}} : use NMODL kinetic equations for the given reactions ; {{--nmodl-depend=VARS}} : specify DEPEND variables for NMODL interpolation tables ; {{--octave[=FILE]}} : write Octave output to file (default: <model-name>.m) ; {{--matlab[=FILE]}} : write Matlab output to file (default: <model-name>.m) ; {{--vclamp-octave[=FILE]}} : write Octave voltage clamp script to file (default: <model-name>_vclamp.m) ; {{--vclamp-hoc[=FILE]}} : write HOC voltage clamp script to file (default: <model-name>.ses) ; {{--debug}} : print additional debugging information ; {{-t}} : use interpolation tables in generated code ; {{-h, --help}} : print help === Model description language The following constructs comprise the model description language: ; '''{{MODEL}}'''{{ ::= }} '''{{INPUT }}''' {''ID''}{{ | }} {''ID''} ['''{{AS }}'''{''LOCAL-ID''}] ['''{{FROM }}'''{''NAMESPACE''}] ... : Declares one or several imported quantities. If the optional '''{{AS}}''' parameter is given, then the quantity is imported as {''LOCAL-ID''}. If the optional '''{{FROM}}''' parameter is given, then the quantity is imported from namespace {''NAMESPACE''}. ; {{ | }} '''{{OUTPUT}}''' {''ID''} : Declares that an existing quantity be exported. ; {{ | }} '''{{CONST}}''' {''ID''} = {''EXPR''} : Declares a constant quantity (its value will be computed at declaration time). ; {{ | }} '''{{FUN}}''' {''ID''} ( {''ARG-ID''} ... ) {''EXPR''} : Declares a function (a parameterized expression with no free variables). ; {{ | }} {''ID''} = {''EXPR''} : Declares an assigned quantity (an expression that can refer to other quantities in the system). ; {{ | }} '''{{REACTION}}''' {''ID''} {''TRANSITIONS''} {''INITIAL-EXPR''} {''OPEN-ID''} : Declares a reaction quantity. See below for the syntax of state transition equations. {''INITIAL-EXPR''} is an expression that computes the initial value. {''OPEN-ID''} is the name of the open state. It must be one of the states defined by the transition equations. ; {{ | }} '''{{COMPONENT}}''' ( '''{{TYPE}}''' {''ID''} ) ( '''{{NAME}}''' {''ID''} ) {''ELEMENTS''} ) : Declares a system component (a quantity that can contain other quantities). ==== Expressions Expressions in the model description language are defined as: ; '''{{EXPR}}'''{{ ::= }} {''NUM''} : A numeric constant. ; {{ | }}{''ID''} : A variable name. ; {{ | }}{''ID''} ( {''EXPR''} ... ) : A function invocation. ; {{ | }}{''EXPR''} {''OP''} {''EXPR''} : Arithmetic operator invocation. The following operators are supported: {{+ - / * > < <= >= ^}} ; {{ | }}'''{{LET}}''' ( {''BINDINGS''} ) {''EXPR''} : Local variables declaration. Each element in {''BINDINGS''} is of the form: ( {''ID''} {''EXPR''} ) ; {{ | }}'''{{IF}}''' {''CONDITION''} '''{{THEN}}''' {''EXPR''} '''{{ELSE}}''' {''EXPR''} : Conditional expression. The expression after '''{{IF}}''' must be a comparison expression. ==== State transition equations State transition equations in the model description language are defined as: ; '''{{TRANSITION}}'''{{ ::= }} '''{{->}}''' {''SRC-ID''} {''DEST-ID''} {''EXPR''} : Declares that a transition occurs from state {''SRC-ID''} to state {''DEST-ID''} at rate computed by {''EXPR''}. ; {{ | }} '''{{<->}}''' {''SRC-ID''} {''DEST-ID''} {''EXPR-1''} {''EXPR-2''} : Declares that a transition occurs from state {''SRC-ID''} to state {''DEST-ID''} and vice versa, at rates computed by {''EXPR-1''} and {''EXPR-2''}. ==== Ionic current definitions Currently, the {{NMODL}} code generator recognizes and generates code for ion channel components that are defined as follows: ; '''{{COMPONENT (TYPE ionic-current) (NAME {NAME})}}''' ( '''{{COMPONENT}}''' ( '''{{TYPE}}''' gate ) ... : One or more gate definitions. Each component of type gate must export the reactions that characterize the gate dynamics. ; '''{{COMPONENT}}''' ( '''{{TYPE}}''' pore ) ... : Conductance law definition. This component must export a constant maximal conductance, or an assigned quantity whose equation represents the conductance law used. ; [ '''{{COMPONENT}}''' ( '''{{TYPE}}''' permeating-ion ) ... ] ; [ '''{{COMPONENT}}''' ( '''{{TYPE}}''' accumulating-substance ) ... ] ==== Hodgkin-Huxley ionic conductance extension The Hodgkin-Huxley ionic conductance extension is a shortcut that declares a reaction corresponding to the Hodgkin-Huxley formulation of ion channel dynamics. ; '''{{HH-IONIC-GATE}}''' : ( {''ION-NAME''} : Ion name: exported variables will be of the form {{{ion}_{id}}}. ; '''{{M-POWER}}''' {''INTEGER''} : Power of state variable {{M}}. ; '''{{H-POWER}}''' {''INTEGER''} : Power of state variable {{H}}. If zero, the initial value and equations for this variable can be omitted. ; '''{{INITIAL-M}}''' {''EXPR''} : Expression that computes initial value for state variable {{M}}. ; '''{{INITIAL-H}}''' {''EXPR''} : Expression that computes initial value for state variable {{H}}. ; '''{{M-ALPHA}}''' {''EXPR''} : Closed state to open state rate expression for state variable {{M}}. ; '''{{M-BETA}}''' {''EXPR''} : Open state to closed state rate expression for state variable {{M}}. ; '''{{H-ALPHA}}''' {''EXPR''} : Closed state to open state rate expression for state variable {{H}}. ; '''{{H-BETA}}''' {''EXPR''} : Open state to closed state rate expression for state variable {{H}}. ; '''{{M-INF}}''' {''EXPR''} : Steady state expression for variable {{M}}. ; '''{{M-TAU}}''' {''EXPR''} : Time constant expression for variable {{M}}. ; '''{{H-INF}}''' {''EXPR''} : Steady state expression for variable {{H}}. ; '''{{H-TAU}}''' {''EXPR''} : Time constant expression for variable {{H}}. == Examples ;; Cerebellar Purkinje Cell: resurgent Na current and high frequency ;; firing (Khaliq et al 2003). nemo-model Khaliq03 input v cai from ion-pools ica from ion-currents const ena = 60 const ek = -88 const ca0 = 1e-4 component (type ionic-current) (name CaBK) ;: BK-type Purkinje calcium-activated potassium current component (type gate) ;; constants const ztau = 1.0 ;; rate functions CaBK_v = (v + 5) minf = (let ((vh -28.9) (k 6.2)) (1.0 / (1.0 + exp (neg ((CaBK_v - vh) / k))))) mtau = (let ((y0 0.000505) (vh1 -33.3) (k1 -10.0) (vh2 86.4) (k2 10.1)) ((1e3) * (y0 + 1 / (exp ((CaBK_v + vh1) / k1) + exp ((CaBK_v + vh2) / k2))))) hinf = (let ((y0 0.085) (vh -32.0) (k 5.8)) (y0 + (1 - y0) / (1 + exp ((CaBK_v - vh) / k)))) htau = (let ((y0 0.0019) (vh1 -54.2) (k1 -12.9) (vh2 48.5) (k2 5.2)) ((1e3) * (y0 + 1 / (exp ((CaBK_v + vh1) / k1) + exp ((CaBK_v + vh2) / k2))))) zinf = (let ((k 0.001)) (1 / (1 + (k / cai)))) z_alpha = (zinf / ztau) z_beta = ((1 - zinf) / ztau) reaction z transitions (<-> O C z_alpha z_beta) conserve (1 = (O + C)) initial (let ((k 0.001)) (1 / (1 + k / ca0))) open O power 2 output z hh-ionic-gate CaBK ;; ion name: exported variables will be of the form {ion}_{id} initial-m (minf) initial-h (hinf) m-power 3 h-power 1 m-inf (minf) m-tau (mtau) h-inf (hinf) h-tau (htau) component (type pore) const gbar_CaBK = 0.007 output gbar_CaBK component (type permeating-ion) (name k) const e_CaBK = ek output e_CaBK ;; end BK current component (type ionic-current) (name CaP) ;; HH P-type Calcium current component (type gate) ;; rate functions inf = (let ((cv -19) (ck 5.5)) (1.0 / (1.0 + exp (neg ((v - cv) / ck))))) tau = ((1e3) * (if (v > -50) then (0.000191 + (0.00376 * exp (neg (((v + 41.9) / 27.8) ^ 2)))) else (0.00026367 + (0.1278 * exp (0.10327 * v))))) hh-ionic-gate CaP ;; ion name: exported variables will be of the form {ion}_{id} initial-m (inf) m-power 1 h-power 0 m-inf inf m-tau tau component (type permeability) fun ghk (v ci co) (let ((F 9.6485e4) (R 8.3145) (T (22 + 273.19)) (Z 2) (E ((1e-3) * v))) (let ((k0 ((Z * (F * E)) / (R * T)))) (let ((k1 (exp (neg (k0)))) (k2 (((Z ^ 2) * (E * (F ^ 2))) / (R * T)))) (1e-6) * (if (abs (1 - k1) < 1e-6) then (Z * F * (ci - (co * k1)) * (1 - k0)) else (k2 * (ci - (co * k1)) / (1 - k1)))))) const pcabar = 0.00005 const cao = 2.4 pca = (pcabar * ghk (v cai cao)) output pca component (type permeating-ion) (name ca) ;; end CaP current component (type ionic-current) (name K1) ;; HH TEA-sensitive Purkinje potassium current component (type gate) ;; constants ;; rate functions K1_v = (v + 11) ;; account for junction potential minf = (let ((mivh -24) (mik 15.4)) (1 / (1 + exp (neg (K1_v - mivh) / mik)))) mtau = (let ((mty0 0.00012851) (mtvh1 100.7) (mtk1 12.9) (mtvh2 -56.0) (mtk2 -23.1)) (1e3 * (if (K1_v < -35) then (3.0 * (3.4225e-5 + 0.00498 * exp (neg (K1_v) / -28.29))) else (mty0 + 1.0 / (exp ((K1_v + mtvh1) / mtk1) + exp ((K1_v + mtvh2) / mtk2))) ))) hinf = (let ((hiy0 0.31) (hiA 0.78) (hivh -5.802) (hik 11.2)) (hiy0 + hiA / (1 + exp ((K1_v - hivh) / hik)))) htau = (1e3 * (if ( K1_v > 0 ) then (0.0012 + 0.0023 * exp (-0.141 * K1_v)) else (1.2202e-05 + 0.012 * exp (neg (((K1_v - (-56.3)) / 49.6) ^ 2))))) hh-ionic-gate K1 ;; ion name: exported variables will be of the form {ion}_{id} initial-m (minf) initial-h (hinf) m-power 3 h-power 1 m-inf (minf) m-tau (mtau) h-inf (hinf) h-tau (htau) component (type pore) const gbar = 0.004 output gbar component (type permeating-ion) (name k) const e = ek output e ;; end K1 current component (type ionic-current) (name K2) ;; HH Low TEA-sensitive Purkinje potassium current component (type gate) ;; constants ;; rate functions K2_v = (v + 11) ;; account for junction potential minf = (let ((mivh -24) (mik 20.4)) (1 / (1 + exp ((neg (K2_v - mivh)) / mik)))) mtau = ((1e3) * (if (K2_v < -20) then (0.000688 + 1 / (exp ((K2_v + 64.2) / 6.5) + exp ((K2_v - 141.5) / -34.8))) else (0.00016 + 0.0008 * exp (-0.0267 * K2_v)))) hh-ionic-gate K2 ;; ion name: exported variables will be of the form {ion}_{id} initial-m (minf) m-power 4 h-power 0 m-inf (minf) m-tau (mtau) component (type pore) const gbar = 0.002 output gbar component (type permeating-ion) (name k) const e = ek output e ;; end K2 current component (type ionic-current) (name K3) ;; HH slow TEA-insensitive Purkinje potassium current component (type gate) ;; constants ;; rate functions K3_v = (v + 11) ;; account for junction potential minf = (let ((mivh -16.5) (mik 18.4)) (1 / (1 + exp ((neg (K3_v - mivh)) / mik)))) mtau = ((1e3) * (0.000796 + 1.0 / (exp ((K3_v + 73.2) / 11.7) + exp ((K3_v - 306.7) / -74.2)))) hh-ionic-gate K3 ;; ion name: exported variables will be of the form {ion}_{id} initial-m (minf) m-power 4 h-power 0 m-inf (minf) m-tau (mtau) component (type pore) const gbar = 0.004 output gbar component (type permeating-ion) (name k) const e = ek output e ;; end K3 current component (type ionic-current) (name Narsg) component (type gate) const Con = 0.005 const Coff = 0.5 const Oon = 0.75 const Ooff = 0.005 const alfac = (pow ((Oon / Con) (1.0 / 4.0))) const btfac = (pow ((Ooff / Coff) (1.0 / 4.0))) const alpha = 150 const beta = 3 const gamma = 150 const delta = 40 const epsilon = 1.75 const zeta = 0.03 const x1 = 20 const x2 = -20 const x3 = 1e12 const x4 = -1e12 const x5 = 1e12 const x6 = -25 ;; rate functions f01 = (4.0 * alpha * exp (v / x1)) f02 = (3.0 * alpha * exp (v / x1)) f03 = (2.0 * alpha * exp (v / x1)) f04 = (alpha * exp (v / x1)) f0O = (gamma * exp (v / x3)) fip = (epsilon * exp (v / x5)) f11 = (4.0 * alpha * alfac * exp (v / x1)) f12 = (3.0 * alpha * alfac * exp (v / x1)) f13 = (2.0 * alpha * alfac * exp (v / x1)) f14 = (alpha * alfac * exp (v / x1)) f1n = (gamma * exp (v / x3)) fi1 = (Con) fi2 = (Con * alfac) fi3 = (Con * alfac * alfac) fi4 = (Con * alfac * alfac * alfac) fi5 = (Con * alfac * alfac * alfac * alfac) fin = (Oon) b01 = (beta * exp (v / x2)) b02 = (2.0 * beta * exp (v / x2)) b03 = (3.0 * beta * exp (v / x2)) b04 = (4.0 * beta * exp (v / x2)) b0O = (delta * exp (v / x4)) bip = (zeta * exp (v / x6)) b11 = (beta * btfac * exp (v / x2)) b12 = (2.0 * beta * btfac * exp (v / x2)) b13 = (3.0 * beta * btfac * exp (v / x2)) b14 = (4.0 * beta * btfac * exp (v / x2)) b1n = (delta * exp (v / x4)) bi1 = (Coff) bi2 = (Coff * btfac) bi3 = (Coff * btfac * btfac) bi4 = (Coff * btfac * btfac * btfac) bi5 = (Coff * btfac * btfac * btfac * btfac) bin = (Ooff) reaction z transitions <-> C1 C2 f01 b01 <-> C2 C3 f02 b02 <-> C3 C4 f03 b03 <-> C4 C5 f04 b04 <-> C5 O f0O b0O <-> O B fip bip <-> O I6 fin bin <-> C1 I1 fi1 bi1 <-> C2 I2 fi2 bi2 <-> C3 I3 fi3 bi3 <-> C4 I4 fi4 bi4 <-> C5 I5 fi5 bi5 <-> I1 I2 f11 b11 <-> I2 I3 f12 b12 <-> I3 I4 f13 b13 <-> I4 I5 f14 b14 <-> I5 I6 f1n b1n conserve (1 = (I1 + I2 + I3 + I4 + I5 + I6 + C1 + C2 + C3 + C4 + C5 + O + B)) open O power 1 output z component (type pore) const gbar = 0.015 output gbar component (type permeating-ion) (name na) const e = ena output e ;; end Narsg component component (type ionic-current) (name Ih) component (type gate) ;; rate functions inf = (1.0 / (1.0 + exp ((v + 90.1) / 9.9))) tau = ((1e3) * (0.19 + 0.72 * exp (neg (((v - (-81.5)) / 11.9) ^ 2)))) hh-ionic-gate Ih ;; ion name: exported variables will be of the form {ion}_{id} initial-m (inf) m-power 1 h-power 0 m-inf (inf) m-tau (tau) component (type pore) const gbar = 0.0001 output gbar component (type permeating-ion) (name non-specific) const e = -30 output e ;; end Ih current component (type ionic-current) (name Leak) component (type pore) const gbar = 5e-5 output gbar component (type permeating-ion) (name non-specific) const e = -60 output e ;; end leak current component (type decaying-pool) (name ca) const F = 96485.0 const ca_depth = 0.1 const ca_beta = 1.0 d (ca) = ((neg (ica) / (2 * ca0 * F * ca_depth)) - ((if (ca < ca0) then ca0 else ca) * ca_beta)) initial ca0 cac = (if (ca < ca0) then ca0 else ca) output cac component (type membrane-capacitance) const C_m = (1e-3) output C_m component (type voltage-clamp) (name K1) const vchold = -71 const vcbase = -69 const vcinc = 10 const vcsteps = 8 const vchdur = 30 const vcbdur = 100 output vchold vcbase vcinc vcsteps vchdur vcbdur == About this egg === Author [[/users/ivan-raikov|Ivan Raikov]] === Version history ; 9.0 : transitioning to {{ersatz}} templates for code generation ; 7.0-8.x : support for the NEST simulator and CVODE solver, discrete events, synaptic components ; 6.11 : bug fix in surface XML generation ; 6.9 : added -p and --surface-xml option ; 6.4-6.8 : bug fixes and enhancements to NMODL code generator ; 6.3 : bug fixes in XML parsing ; 6.2 : supported for deployment as a self-contained package ; 6.0-6.1 : introduced indentation-based syntax ; 5.0-5.1 : Added some flexibility in generating HH rate equations ; 4.4 : Voltage clamp script generation ; 4.3 : Renamed permeating-substance components to permeating-ion ; 4.2 : Using installation-chicken-home to install example files ; 4.1 : Documentation converted to wiki format ; 4.0 : Introducing the gate-complex element ; 3.4 : Documentation update ; 3.1-3.3 : Fixes to the examples ; 3.0 : Internal restructuring and new examples ; 2.5 : Bug fixes in option handling and NMODL backend ; 2.4 : Converted to using getopt-long ; 2.3 : Added eggdoc as a dependency ; 2.2 : Added stx-engine.scm to file manifest ; 2.1 : Ported to Chicken 4 ; 2.0 : Introduced functors ; 1.15 : Added nmodl-depend option ; 1.14 : Added support for exponential Euler integration ; 1.13 : Change in the integration method used for the AKP example ; 1.12 : Added support for binary conductances and conservation equations ; 1.11 : Bug fixes in the current equations part of NMODL code generator ; 1.10 : AKP06 example is now installed in CHICKEN-HOME/nemo/examples ; 1.9 : Documentation and example updates ; 1.8 : Bug fixes related to kinetic equation processing ; 1.6 : Added infix expression parser (nemo format) ; 1.0 : Initial release === License Copyright 2008-2014 Ivan Raikov This program is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. A full copy of the GPL license can be found at <http://www.gnu.org/licenses/>. Description of your changes:

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