// nFit
// (c) Charles CH Cohen, 2014-present
// this software is released to the public under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
// International license (CC BY-NC-ND 4.0, in English).
// for any questions, please email c.cohen@gmx.com
//---------------------Parameter definitions and initial values---------------------
// Define and set initial (expected) values for each parameter, as well as upper and
// lower bounds.
// ---------------------------------------------------------------------------------
// ---------------------------Passive Parameters------------------------------------
// ----------------------------Axial resistance-------------------------------------
// Intracellular axial resistivity, or Ri. Unit = ohm cm.
Ri_def = 200
// The initial value is set to the default
Ri = Ri_def
// from estimated resistivity of mammalian cerebrospinal fluid at 35 C
// (Moffitt et al. 2005)
Ri_low = 50
// based on highest measured intracellular resistivity (Major et al. 1994).
Ri_high = 400
// norm values; only for optimized variables
Ri_norm_def = Ri_def/Ri_low
Ri_norm = Ri/Ri_low
Ri_low_norm = Ri_low/Ri_low
Ri_high_norm = Ri_high/Ri_low
// ---------------------------------------------------------------------------------
// Periaxonal axial resistance, or rpa. This refers to the submyelin, extra-
// axonal resistance. Unit = Mega ohm / cm.
rpa_def = 1e5
// initial value
rpa = rpa_def
// rpa_low
// rpa_low = 5e3
rpa_low = 6e4
// rpa_high
rpa_high = 2.5e7
// rpa_high = 9e6
// norm values
rpa_norm_def = rpa_def/rpa_low
rpa_norm = rpa/rpa_low
rpa_low_norm = rpa_low/rpa_low
rpa_high_norm = rpa_high/rpa_low
// ---------------------------------------------------------------------------------
// Extracellular space axial resistance (rext). Unit = Mega ohm / cm. Fixed.
// Based on Ri_low and the cross-sectional area of the extracellular bath space
// (sphere 4 cm in diameter).
rext = 1e-6
// ---------------------------------------------------------------------------------
// Intra-pipette axial resistivity, calculated as bridge balance of the electrode
// factored by the ratio between the total cross-sectional area to length of the
// modellled pipette tip. Since bridge balance may vary between electrodes, this is
// determined individually for each cell based on the bridge balance entered at setup.
// ---------------------------------------------------------------------------------
// ---------------------------Membrane resistance-----------------------------------
// Cellular membrane specific resistance, Rm. Refers to the ions flowing through
// passive membrane leak channels. Unit = ohm cm^2.
Rm_def = 25000
// initial value
Rm = Rm_def
// Lowest estimated Rm (Tasaki 1955).
// Rm_low = 100
// Based on lowest estimated Rm for oligodendrocytes (Bakiri et al. 2011, Chan et al. 2013)
Rm_low = 2e3
// Based on Rm highest reported by Major et al. 1994.
// Rm_high = 2e5
// Based on Alle and Geiger 2006.
Rm_high = 6e4
// norm values
Rm_norm_def = Rm_def/Rm_low
Rm_norm = Rm/Rm_low
Rm_low_norm = Rm_low/Rm_low
Rm_high_norm = Rm_high/Rm_low
// ---------------------------------------------------------------------------------
// Myelin sheath specific resistance. Unit = ohm cm^2
Rmy_def = 1e5
// initial value
Rmy = Rmy_def
// Based on a minimum of 10 myelin membranes at 2 kOhm cm2, the lowest reported
// membrane resistance in precursor and mature oligos (Chan et al. 2013 and Bakiri
// et al. 2011)
Rmy_low = 20000
// Based on a maximum of 100 myelin membranes at highest estimated Rmm (Bakiri et al. 2011).
Rmy_high = 1.6e6
// Rmy_high = 2.4e6
// norm values
Rmy_norm_def = Rmy_def/Rmy_low
Rmy_norm = Rmy/Rmy_low
Rmy_low_norm = Rmy_low/Rmy_low
Rmy_high_norm = Rmy_high/Rmy_low
// ---------------------------------------------------------------------------------
// Specific surface resistance of extracellular space, Rext (unit = ohm cm^2). Based
// on Ri_low converted to surface units. Dependent upon local surface area
// enveloping neuronal processes (~10^-6 cm^2) and length (10^-2 cm).
Rext = 1e-8
// ---------------------------------------------------------------------------------
// Pipette surface specific resistance. Based on the resistive properties of
// the borosilicate glass used (see methods and Ehrt 2009). Fixed.
Rpip = 5e10
// ---------------------------------------------------------------------------------
// ---------------------------Membrane capacitance----------------------------------
// Neural membrane specific capacitance. Unit = uF / cm^2.
Cm_def = 1
// initial value
Cm = Cm_def
// Based on some of the lowest estimated values for Cm
// (Major et al. 1994 or Eyal et al. 2016)
Cm_low = 0.5
// Refers to one of the highest estimated values for Cm (Rapp et al. 1994)
Cm_high = 2
// norm values
Cm_norm_def = Cm_def/Cm_low
Cm_norm = Cm/Cm_low
Cm_low_norm = Cm_low/Cm_low
Cm_high_norm = Cm_high/Cm_low
// ---------------------------------------------------------------------------------
// Myelin sheath specific capacitance. Unit = uF / cm^2.
Cmy_def = 0.05
// initial value
Cmy = Cmy_def
// Based on a maximum of 100 myelin membranes at Cm_low.
Cmy_low = 0.005
// Based on minimum of 1 myelin membrane at Cm_high
Cmy_high = 0.2
// norm values
Cmy_norm_def = Cmy_def/Cmy_low
Cmy_norm = Cmy/Cmy_low
Cmy_low_norm = Cmy_low/Cmy_low
Cmy_high_norm = Cmy_high/Cmy_low
// ---------------------------------------------------------------------------------
// Specific surface capacitance of extracellular space, Cext (unit = ohm cm^2).
// Counterpart to Rext. Fixed.
Cext = 0
// ---------------------------------------------------------------------------------
// Specific surface capacitance of borosilicate glass patch pipettes. Pipettes will
// be modelled directly, like cellular compartments, to account for their
// electrotonic contribution in passive, subthreshold recordings (Roth and Hausser
// 2001). Even in well-compensated settings, pipette capacitance can have a small
// effect on the cellular response (Major et al. 1994). Therefore, in addition
// to creating morphologically and biophysically accurate pipette tips (see methods),
// leftover pipette capacitance will be optimized out, to parse it from cellular
// capacitances. Moreover, pipette capacitance may be on the order of myelin sheath
// capacitance (See Methods). Since pipette artifacts are primarily from the injecting
// recording electrode, only that pipette's capacitance will be optimized out.
// Unit = uF / cm^2.
Cpip_def = 1.29e-6
// initial value
Cpip = Cpip_def
Cpip_low = 1.29e-8
Cpip_high = 1.29e-4
// norm values
Cpip_norm_def = Cpip_def/Cpip_low
Cpip_norm = Cpip/Cpip_low
Cpip_low_norm = Cpip_low/Cpip_low
Cpip_high_norm = Cpip_high/Cpip_low
// ---------------------------------------------------------------------------------
// ----------------------------Paranodal factors------------------------------------
// average paranodal delta estimated from Rosenbluth et al 2013 (nm)
paradelta = 2.6
// consequent rpafact, or factor for rpa at paranodes given paradelta (eq. 5)
parafact_def = 4.7
parafact = parafact_def
parafact_low = 1
parafact_high = 100
// norm values
parafact_norm_def = parafact_def/parafact_low
parafact_norm = parafact/parafact_low
parafact_low_norm = parafact_low/parafact_low
parafact_high_norm = parafact_high/parafact_low
// ---------------------------------------------------------------------------------
// ------------------------------Alternatives---------------------------------------
// Alternative implementations of some axonal parameters to robustly test the single
// cable. Available options include:
// RmNode: a separate nodal membrane resistance parameter, to account for possibly
// very low nodal membrane resistance (Tasaki 1955), or membrane channel blockers
// possibly not fully blocking nodal membranes.
// RmAxon: a separate axonal membrane resistance (no expected basis)
// RmInt: a separate internodal axon membrane resistance, to account for bath-applied
// membrane channel blockers possibly not reaching under the myelin.
// RiAxon: a separate intra-axonal resistivity parameter (no biophysical basis)
RmN_def = Rm_def
RmN = Rm
RmN_low = Rm_low
RmN_high = Rm_high
RmN_norm_def = RmN_def/RmN_low
RmN_norm = RmN/RmN_low
RmN_low_norm = RmN_low/RmN_low
RmN_high_norm = RmN_high/RmN_low
RmA_def = Rm_def
RmA = Rm
RmA_low = Rm_low
RmA_high = Rm_high
RmA_norm_def = RmA_def/RmA_low
RmA_norm = RmA/RmA_low
RmA_low_norm = RmA_low/RmA_low
RmA_high_norm = RmA_high/RmA_low
RmI_def = Rm_def
RmI = Rm
RmI_low = Rm_low
RmI_high = Rm_high
RmI_norm_def = RmI_def/RmI_low
RmI_norm = RmI/RmI_low
RmI_low_norm = RmI_low/RmI_low
RmI_high_norm = RmI_high/RmI_low
RiA_def = Ri_def
RiA = Ri
RiA_low = Ri_low
RiA_high = Ri_high
RiA_norm_def = RiA_def/RiA_low
RiA_norm = RiA/RiA_low
RiA_low_norm = RiA_low/RiA_low
RiA_high_norm = RiA_high/RiA_low
// ---------------------------------------------------------------------------------
// -------------------------------Batteries-----------------------------------------
// Intracellular voltage gradient powering bioelectric cells. With respect to
// extracellular space (= 0). Units = mV.
v_init = getRMP()
// The extracellular battery. eext is fixed.
eext = 0
// ---------------------------------------------------------------------------------
// ------------------------------uselogs---------------------------------------------
// uselog refers to whether a parameter will be optimized in logspace.
Ri_uselog = 1
rpa_uselog = 1
parafact_uselog = 1
Rm_uselog = 1
Rmy_uselog = 1
Cm_uselog = 1
Cmy_uselog = 1
RmN_uselog = 1
RmA_uselog = 1
RmI_uselog = 1
RiA_uselog = 1
Cpip_uselog = 1
// ---------------------------------------------------------------------------------
// ------------------------------doargs---------------------------------------------
// Decide whether a parameter should be a fit variable (in a given simulation type)
Ri_doarg = 1
rpa_doarg = 1
parafact_doarg = 1
Rm_doarg = 1
Rmy_doarg = 1
Cm_doarg = 1
Cmy_doarg = 1
Cpip_doarg = 1
RmN_doarg = 0
RmA_doarg = 0
RmI_doarg = 0
RiA_doarg = 0
per_int_doarg = 0
exp_doarg = 0
// ---------------------------------------------------------------------------------
// ---------------------------------------------------------------------------------
// -------------------------Active Parameters---------------------------------------
// --------------------------Sodium channels----------------------------------------
// Na channel expression. Units pS/cm2.
Na_de_low = 0.01
Na_de_high = 100
Na_de_def = 30
Na_de = Na_de_def
Na_de_norm_def = Na_de_def/Na_de_low
Na_de_norm = Na_de/Na_de_low
Na_de_low_norm = Na_de_low/Na_de_low
Na_de_high_norm = Na_de_high/Na_de_low
Na_so_low = 0.01
Na_so_high = 2000
Na_so_def = 600
Na_so = Na_so_def
Na_so_norm_def = Na_so_def/Na_so_low
Na_so_norm = Na_so/Na_so_low
Na_so_low_norm = Na_so_low/Na_so_low
Na_so_high_norm = Na_so_high/Na_so_low
Na_prox_low = 0.01
Na_prox_high = 10000
Na_prox_def = 1000
Na_prox = Na_prox_def
Na_prox_norm_def = Na_prox_def/Na_prox_low
Na_prox_norm = Na_prox/Na_prox_low
Na_prox_low_norm = Na_prox/Na_prox_low
Na_prox_high_norm = Na_prox_high/Na_prox_low
Na_ais_low = 0.01
Na_ais_high = 50000
Na_ais_def = 10000
Na_ais = Na_ais_def
Na_ais_norm_def = Na_ais_def/Na_ais_low
Na_ais_norm = Na_ais/Na_ais_low
Na_ais_low_norm = Na_ais_low/Na_ais_low
Na_ais_high_norm = Na_ais_high/Na_ais_low
Na_int_low = 0.01
Na_int_high = 1000
Na_int_def = 100
Na_int = Na_int_def
Na_int_norm_def = Na_int_def/Na_int_low
Na_int_norm = Na_int/Na_int_low
Na_int_low_norm = Na_int_low/Na_int_low
Na_int_high_norm = Na_int_high/Na_int_low
Na_nod_low = Na_ais_low
Na_nod_high = Na_ais_high
Na_nod_def = Na_ais_def
Na_nod = Na_ais
Na_nod_norm_def = Na_nod_def/Na_nod_low
Na_nod_norm = Na_nod/Na_nod_low
Na_nod_low_norm = Na_nod_low/Na_nod_low
Na_nod_high_norm = Na_nod_high/Na_nod_low
Na_end_low = 0.01
Na_end_high = 50000
Na_end_def = 400
Na_end = Na_end_def
Na_end_norm_def = Na_end_def/Na_end_low
Na_end_norm = Na_end/Na_end_low
Na_end_low_norm = Na_end_low/Na_end_low
Na_end_high_norm = Na_end_high/Na_end_low
Na_col_low = 0.01
Na_col_high = 1000
Na_col_def = 200
Na_col = Na_col_def
Na_col_norm_def = Na_col_def/Na_col_low
Na_col_norm = Na_col/Na_col_low
Na_col_low_norm = Na_col_low/Na_col_low
Na_col_high_norm = Na_col_high/Na_col_low
Nap_ais_low = 1e-6
Nap_ais_high = 100
Nap_ais_def = 1
Nap_ais = Nap_ais_def
Nap_ais_norm_def = Nap_ais_def/Nap_ais_low
Nap_ais_norm = Nap_ais/Nap_ais_low
Nap_ais_low_norm = Nap_ais_low/Nap_ais_low
Nap_ais_high_norm = Nap_ais_high/Nap_ais_low
Nap_int_low = 1e-6
Nap_int_high = 10
Nap_int_def = 1e-2
Nap_int = Nap_int_def
Nap_int_norm_def = Nap_int_def/Nap_int_low
Nap_int_norm = Nap_int/Nap_int_low
Nap_int_low_norm = Nap_int_low/Nap_int_low
Nap_int_high_norm = Nap_int_high/Nap_int_low
Nap_nod_low = Nap_ais_low
Nap_nod_high = Nap_ais_high
Nap_nod_def = Nap_ais_def
Nap_nod = Nap_nod_def
Nap_nod_norm_def = Nap_nod_def/Nap_nod_low
Nap_nod_norm = Nap_nod/Nap_nod_low
Nap_nod_low_norm = Nap_nod_low/Nap_nod_low
Nap_nod_high_norm = Nap_nod_high/Nap_nod_low
Nap_end_low = 1e-6
Nap_end_high = 100
Nap_end_def = 1e-1
Nap_end = Nap_end_def
Nap_end_norm_def = Nap_end_def/Nap_end_low
Nap_end_norm = Nap_end/Nap_end_low
Nap_end_low_norm = Nap_end_low/Nap_end_low
Nap_end_high_norm = Nap_end_high/Nap_end_low
// ---------------------------------------------------------------------------------
// -------------------------Potassium channels--------------------------------------
// Potassium channel expression. Units pS/cm2.
Kv1_de_low = 0.01
Kv1_de_high = 100
Kv1_de_def = 40
Kv1_de = Kv1_de_def
Kv1_de_norm_def = Kv1_de_def/Kv1_de_low
Kv1_de_norm = Kv1_de/Kv1_de_low
Kv1_de_low_norm = Kv1_de_low/Kv1_de_low
Kv1_de_high_norm = Kv1_de_high/Kv1_de_high
Kv1_so_low = 0.01
Kv1_so_high = 1000
Kv1_so_def = 100
Kv1_so = Kv1_so_def
Kv1_so_norm_def = Kv1_so_def/Kv1_so_low
Kv1_so_norm = Kv1_so/Kv1_so_low
Kv1_so_low_norm = Kv1_so_low/Kv1_so_low
Kv1_so_high_norm = Kv1_so_high/Kv1_so_low
Kv1_prox_low = 0.01
Kv1_prox_high = 4000
Kv1_prox_def = 200
Kv1_prox = Kv1_prox_def
Kv1_prox_norm_def = Kv1_prox_def/Kv1_prox_low
Kv1_prox_norm = Kv1_prox/Kv1_prox_low
Kv1_prox_low_norm = Kv1_prox_low/Kv1_prox_low
Kv1_prox_high_norm = Kv1_prox_high/Kv1_prox_low
Kv1_ais_low = 0.01
Kv1_ais_high = 10000
Kv1_ais_def = 3000
Kv1_ais = Kv1_ais_def
Kv1_ais_norm_def = Kv1_ais_def/Kv1_ais_low
Kv1_ais_norm = Kv1_ais/Kv1_ais_low
Kv1_ais_low_norm = Kv1_ais_low/Kv1_ais_low
Kv1_ais_high_norm = Kv1_ais_high/Kv1_ais_low
Kv1_int_low = 0.01
Kv1_int_high = 10000
Kv1_int_def = 100
Kv1_int = Kv1_int_def
Kv1_int_norm_def = Kv1_int_def/Kv1_int_low
Kv1_int_norm = Kv1_int/Kv1_int_low
Kv1_int_low_norm = Kv1_int_low/Kv1_int_low
Kv1_int_high_norm = Kv1_int_high/Kv1_int_low
Kv1_nod_low = Kv1_ais_low
Kv1_nod_high = Kv1_ais_high
Kv1_nod_def = Kv1_ais_def
Kv1_nod = Kv1_nod_def
Kv1_nod_norm_def = Kv1_nod_def/Kv1_nod_low
Kv1_nod_norm = Kv1_nod/Kv1_nod_low
Kv1_nod_norm_low = Kv1_nod_low/Kv1_nod_low
Kv1_nod_norm_high = Kv1_nod_high/Kv1_nod_low
Kv1_end_low = 0.01
Kv1_end_high = Kv1_nod_high
Kv1_end_def = 600
Kv1_end = Kv1_end_def
Kv1_end_norm_def = Kv1_end_def/Kv1_end_low
Kv1_end_norm = Kv1_end/Kv1_end_low
Kv1_end_norm_low = Kv1_end_low/Kv1_end_low
Kv1_end_norm_high = Kv1_end_high/Kv1_end_low
Kv1_col_low = 0.01
Kv1_col_high = 2000
Kv1_col_def = 300
Kv1_col = Kv1_col_def
Kv1_col_norm_def = Kv1_col_def/Kv1_col_low
Kv1_col_norm = Kv1_col/Kv1_col_low
Kv1_col_norm_low = Kv1_col_low/Kv1_col_low
Kv1_col_norm_high = Kv1_col_high/Kv1_col_low
// also known as Kv_slow
Kv_de_low = 0.01
Kv_de_high = 100
Kv_de_def = 1
Kv_de = Kv_de_def
Kv_de_norm_def = Kv_de_def/Kv_de_low
Kv_de_norm = Kv_de/Kv_de_low
Kv_de_norm_low = Kv_de_low/Kv_de_low
Kv_de_norm_high = Kv_de_high/Kv_de_low
Kv_so_low = 0.01
Kv_so_high = 1000
Kv_so_def = 25
Kv_so = Kv_so_def
Kv_so_norm_def = Kv_so_def/Kv_so_low
Kv_so_norm = Kv_so/Kv_so_low
Kv_so_norm_low = Kv_so_low/Kv_so_low
Kv_so_norm_high = Kv_so_high/Kv_so_low
Kv7_de_low = 0.01
Kv7_de_high = 100
Kv7_de_def = 15
Kv7_de = Kv7_de_def
Kv7_de_norm_def = Kv7_de_def/Kv7_de_low
Kv7_de_norm = Kv7_de/Kv7_de_low
Kv7_de_norm_low = Kv7_de_low/Kv7_de_low
Kv7_de_norm_high = Kv7_de_high/Kv7_de_low
Kv7_so_low = 0.01
Kv7_so_high = 100
Kv7_so_def = 25
Kv7_so = Kv7_so_def
Kv7_so_norm_def = Kv7_so_def/Kv7_so_low
Kv7_so_norm = Kv7_so/Kv7_so_low
Kv7_so_norm_low = Kv7_so_low/Kv7_so_low
Kv7_so_norm_high = Kv7_so_high/Kv7_so_low
Kv7_prox_low = 0.01
Kv7_prox_high = 500
Kv7_prox_def = 120
Kv7_prox = Kv7_prox_def
Kv7_prox_norm_def = Kv7_prox_def/Kv7_prox_low
Kv7_prox_norm = Kv7_prox/Kv7_prox_low
Kv7_prox_norm_low = Kv7_prox_low/Kv7_prox_low
Kv7_prox_norm_high = Kv7_prox_high/Kv7_prox_low
Kv7_ais_low = 0.01
Kv7_ais_high = 1000
Kv7_ais_def = 160
Kv7_ais = Kv7_ais_def
Kv7_ais_norm_def = Kv7_ais_def/Kv7_ais_low
Kv7_ais_norm = Kv7_ais/Kv7_ais_low
Kv7_ais_norm_low = Kv7_ais_low/Kv7_ais_low
Kv7_ais_norm_high = Kv7_ais_high/Kv7_ais_low
Kv7_int_low = 0.01
Kv7_int_high = 100
Kv7_int_def = 5
Kv7_int = Kv7_int_def
Kv7_int_norm_def = Kv7_int_def/Kv7_int_low
Kv7_int_norm = Kv7_int/Kv7_int_low
Kv7_int_norm_low = Kv7_int_low/Kv7_int_low
Kv7_int_norm_high = Kv7_int_high/Kv7_int_low
Kv7_nod_low = Kv7_ais_low
Kv7_nod_high = Kv7_ais_high
Kv7_nod_def = 160
Kv7_nod = Kv7_nod_def
Kv7_nod_low = Kv7_ais_low
Kv7_nod_norm_def = Kv7_nod_def/Kv7_nod_low
Kv7_nod_norm = Kv7_nod/Kv7_nod_low
Kv7_nod_norm_low = Kv7_nod_low/Kv7_nod_low
Kv7_nod_norm_high = Kv7_nod_high/Kv7_nod_low
Kv7_end_low = 0.01
Kv7_end_high = 1000
Kv7_end_def = 5
Kv7_end = Kv7_end_def
Kv7_end_norm_def = Kv7_end_def/Kv7_end_low
Kv7_end_norm = Kv7_end/Kv7_end_low
Kv7_end_norm_low = Kv7_end_low/Kv7_end_low
Kv7_end_norm_high = Kv7_end_high/Kv7_end_low
Kv7_col_low = 0.01
Kv7_col_high = 100
Kv7_col_def = 5
Kv7_col = Kv7_col_def
Kv7_col_norm_def = Kv7_col_def/Kv7_col_low
Kv7_col_norm = Kv7_col/Kv7_col_low
Kv7_col_norm_low = Kv7_col_low/Kv7_col_low
Kv7_col_norm_high = Kv7_col_high/Kv7_col_low
KCa_low = 0.01
KCa_high = 100
KCa_def = 2
KCa = KCa_def
KCa_norm_def = KCa_def/KCa_low
KCa_norm = KCa/KCa_low
KCa_norm_low = KCa_low/KCa_low
KCa_norm_high = KCa_high/KCa_low
// KCa_de_low = 1e-4
// KCa_de_high = 100
// KCa_de_def = 2
// KCa_de = KCa_de_def
// KCa_de_norm_def = KCa_de_def/KCa_de_low
// KCa_de_norm = KCa_de/KCa_de_low
// KCa_de_norm_low = KCa_de_low/KCa_de_low
// KCa_de_norm_high = KCa_de_high/KCa_de_low
// KCa_so_low = 1e-4
// KCa_so_high = 1000
// KCa_so_def = 2
// KCa_so = KCa_so_def
// KCa_so_norm_def = KCa_so_def/KCa_so_low
// KCa_so_norm = KCa_so/KCa_so_low
// KCa_so_norm_low = KCa_so_low/KCa_so_low
// KCa_so_norm_high = KCa_so_high/KCa_so_low
// KCa_ais_low = 1e-4
// KCa_ais_high = 1000
// KCa_ais_def = 2
// KCa_ais = KCa_ais_def
// KCa_ais_norm_def = KCa_ais_def/KCa_ais_low
// KCa_ais_norm = KCa_ais/KCa_ais_low
// KCa_ais_norm_low = KCa_ais_low/KCa_ais_low
// KCa_ais_norm_high = KCa_ais_high/KCa_ais_low
// KCa_int_low = 1e-4
// KCa_int_high = 100
// KCa_int_def = 2
// KCa_int = KCa_int_def
// KCa_int_norm_def = KCa_int_def/KCa_int_low
// KCa_int_norm = KCa_int/KCa_int_low
// KCa_int_norm_low = KCa_int_low/KCa_int_low
// KCa_int_norm_high = KCa_int_high/KCa_int_low
// KCa_nod_low = 1e-4
// KCa_nod_high = 1000
// KCa_nod_def = 2
// KCa_nod = KCa_nod_def
// KCa_nod_norm_def = KCa_nod_def/KCa_nod_low
// KCa_nod_norm = KCa_nod/KCa_nod_low
// KCa_nod_norm_low = KCa_nod_low/KCa_nod_low
// KCa_nod_norm_high = KCa_nod_high/KCa_nod_low
// KCa_end_low = 1e-4
// KCa_end_high = 1000
// KCa_end_def = 2
// KCa_end = KCa_end_def
// KCa_end_norm_def = KCa_end_def/KCa_end_low
// KCa_end_norm = KCa_end/KCa_end_low
// KCa_end_norm_low = KCa_end_low/KCa_end_low
// KCa_end_norm_high = KCa_end_high/KCa_end_low
// KCa_col_low = 1e-4
// KCa_col_high = 100
// KCa_col_def = 2
// KCa_col = KCa_col_def
// KCa_col_norm_def = KCa_col_def/KCa_col_low
// KCa_col_norm = KCa_col/KCa_col_low
// KCa_col_norm_low = KCa_col_low/KCa_col_low
// KCa_col_norm_high = KCa_col_high/KCa_col_low
// ---------------------------------------------------------------------------------
// ---------------------------Calcium channels--------------------------------------
// Calcium channel expression. Units pS/cm2.
Ca_low = 0.01
Ca_high = 100
Ca_def = 3
Ca = Ca_def
Ca_norm_def = Ca_def/Ca_low
Ca_norm = Ca/Ca_low
Ca_norm_low = Ca_low/Ca_low
Ca_norm_high = Ca_high/Ca_low
// Ca_de_low = 1e-4
// Ca_de_high = 100
// Ca_de_def = 3
// Ca_de = Ca_de_def
// Ca_de_norm_def = Ca_de_def/Ca_de_low
// Ca_de_norm = Ca_de/Ca_de_low
// Ca_de_norm_low = Ca_de_low/Ca_de_low
// Ca_de_norm_high = Ca_de_high/Ca_de_low
// Ca_so_low = 1e-4
// Ca_so_high = 1000
// Ca_so_def = 3
// Ca_so = Ca_so_def
// Ca_so_norm_def = Ca_so_def/Ca_so_low
// Ca_so_norm = Ca_so/Ca_so_low
// Ca_so_norm_low = Ca_so_low/Ca_so_low
// Ca_so_norm_high = Ca_so_high/Ca_so_low
// Ca_ais_low = 1e-4
// Ca_ais_high = 1000
// Ca_ais_def = Ca_so_def
// Ca_ais = Ca_ais_def
// Ca_ais_norm_def = Ca_ais_def/Ca_ais_low
// Ca_ais_norm = Ca_ais/Ca_ais_low
// Ca_ais_norm_low = Ca_ais_low/Ca_ais_low
// Ca_ais_norm_high = Ca_ais_high/Ca_ais_low
// Ca_int_low = 1e-4
// Ca_int_high = 100
// Ca_int_def = 2
// Ca_int = Ca_int_def
// Ca_int_norm_def = Ca_int_def/Ca_int_low
// Ca_int_norm = Ca_int/Ca_int_low
// Ca_int_norm_low = Ca_int_low/Ca_int_low
// Ca_int_norm_high = Ca_int_high/Ca_int_low
// Ca_nod_low = Ca_ais_low
// Ca_nod_high = Ca_ais_high
// Ca_nod_def = Ca_ais_def
// Ca_nod = Ca_nod_def
// Ca_nod_norm_def = Ca_nod_def/Ca_nod_low
// Ca_nod_norm = Ca_nod/Ca_nod_low
// Ca_nod_norm_low = Ca_nod_low/Ca_nod_low
// Ca_nod_norm_high = Ca_nod_high/Ca_nod_low
// Ca_end_low = 1e-4
// Ca_end_high = 1000
// Ca_end_def = Ca_nod_def
// Ca_end = Ca_end_def
// Ca_end_norm_def = Ca_end_def/Ca_end_low
// Ca_end_norm = Ca_end/Ca_end_low
// Ca_end_norm_low = Ca_end_low/Ca_end_low
// Ca_end_norm_high = Ca_end_high/Ca_end_low
// Ca_col_low = 1e-4
// Ca_col_high = 100
// Ca_col_def = Ca_end_def
// Ca_col = Ca_col_def
// Ca_col_norm_def = Ca_col_def/Ca_col_low
// Ca_col_norm = Ca_col/Ca_col_low
// Ca_col_norm_low = Ca_col_low/Ca_col_low
// Ca_col_norm_high = Ca_col_high/Ca_col_low
It2_low = Ca_low
It2_high = Ca_high
It2_def = Ca_def
It2 = It2_def
It2_norm_def = It2_def/It2_low
It2_norm = It2/It2_low
It2_norm_low = It2_low/It2_low
It2_norm_high = It2_high/It2_low
// It2_de_low = Ca_de_low
// It2_de_high = Ca_de_high
// It2_de_def = Ca_de_def
// It2_de = It2_de_def
// It2_de_norm_def = It2_de_def/It2_de_low
// It2_de_norm = It2_de/It2_de_low
// It2_de_norm_low = It2_de_low/It2_de_low
// It2_de_norm_high = It2_de_high/It2_de_low
// It2_so_low = Ca_so_low
// It2_so_high = Ca_so_high
// It2_so_def = Ca_so_def
// It2_so = It2_so_def
// It2_so_norm_def = It2_so_def/It2_so_low
// It2_so_norm = It2_so/It2_so_low
// It2_so_norm_low = It2_so_low/It2_so_low
// It2_so_norm_high = It2_so_high/It2_so_low
// It2_ais_low = Ca_ais_low
// It2_ais_high = Ca_ais_high
// It2_ais_def = Ca_ais_def
// It2_ais = It2_ais_def
// It2_ais_norm_def = It2_ais_def/It2_ais_low
// It2_ais_norm = It2_ais/It2_ais_low
// It2_ais_norm_low = It2_ais_low/It2_ais_low
// It2_ais_norm_high = It2_ais_high/It2_ais_low
// It2_int_low = Ca_int_low
// It2_int_high = Ca_int_high
// It2_int_def = Ca_int_def
// It2_int = It2_int_def
// It2_int_norm_def = It2_int_def/It2_int_low
// It2_int_norm = It2_int/It2_int_low
// It2_int_norm_low = It2_int_low/It2_int_low
// It2_int_norm_high = It2_int_high/It2_int_low
// It2_nod_low = Ca_nod_low
// It2_nod_high = Ca_nod_high
// It2_nod_def = Ca_nod_def
// It2_nod = Ca_nod
// It2_nod_norm_def = It2_nod_def/It2_nod_low
// It2_nod_norm = It2_nod/It2_nod_low
// It2_nod_norm_low = It2_nod_low/It2_nod_low
// It2_nod_norm_high = It2_nod_high/It2_nod_low
// It2_end_low = Ca_end_low
// It2_end_high = Ca_end_high
// It2_end_def = Ca_end_def
// It2_end = It2_end_def
// It2_end_norm_def = It2_end_def/It2_end_low
// It2_end_norm = It2_end/It2_end_low
// It2_end_norm_low = It2_end_low/It2_end_low
// It2_end_norm_high = It2_end_high/It2_end_low
// It2_col_low = Ca_col_low
// It2_col_high = Ca_col_high
// It2_col_def = Ca_col_def
// It2_col = It2_col_def
// It2_col_norm_def = It2_col_def/It2_col_low
// It2_col_norm = It2_col/It2_col_low
// It2_col_norm_low = It2_col_low/It2_col_low
// It2_col_norm_high = It2_col_high/It2_col_low
// ---------------------------------------------------------------------------------
// ------------------------------H channels-----------------------------------------
H_so_def = 1e-4
H_so = H_so_def
H_so_low = 1e-6
H_so_high = 1e-2
H_so_norm_def = H_so_def/H_so_low
H_so_norm = H_so/H_so_low
H_so_norm_low = H_so_low/H_so_low
H_so_norm_high = H_so_high/H_so_low
H_ax_def = 1e-4
H_ax = H_ax_def
H_ax_low = H_so_low
H_ax_high = H_so_high
H_ax_norm_def = H_ax_def/H_ax_low
H_ax_norm = H_so/H_ax_low
H_ax_norm_low = H_ax_low/H_ax_low
H_ax_norm_high = H_ax_high/H_ax_low
// ---------------------------------------------------------------------------------
// ---------------------------Misc constants----------------------------------------
// Constants for linear distribution of dendritic Na and exponential distribution
// of Kv and Kv1 (Keren et al 2009, JPhysiol, 587:1413-37), and exponential
// distribution of H (Kole et al 2006).
Hoff = 0
tauh = 3e-3
maxdist_Na_apic_def = 260
maxdist_Na_apic = maxdist_Na_apic_def
// maxdist_Na_apic_low = 10
// maxdist_Na_apic_high = 800
// maxdist_Na_apic_norm_def = maxdist_Na_apic_def/maxdist_Na_apic_low
// maxdist_Na_apic_norm = maxdist_Na_apic/maxdist_Na_apic_low
// maxdist_Na_apic_norm_low = maxdist_Na_apic_low/maxdist_Na_apic_low
// maxdist_Na_apic_norm_high = maxdist_Na_apic_high/maxdist_Na_apic_low
maxdist_Na_bas_def = 200
maxdist_Na_bas = maxdist_Na_bas_def
// maxdist_Na_bas_low = 10
// maxdist_Na_bas_high = 400
// maxdist_Na_bas_norm_def = maxdist_Na_bas_def/maxdist_Na_bas_low
// maxdist_Na_bas_norm = maxdist_Na_bas/maxdist_Na_bas_low
// maxdist_Na_bas_norm_low = maxdist_Na_bas_low/maxdist_Na_bas_low
// maxdist_Na_bas_norm_high = maxdist_Na_bas_high/maxdist_Na_bas_low
lc_Kv_Kv1_def = 250
lc_Kv_Kv1 = lc_Kv_Kv1_def
// lc_Kv_Kv1_low = 10
// lc_Kv_Kv1_high = 800
// lc_Kv_Kv1_norm_def = lc_Kv_Kv1_def/lc_Kv_Kv1_low
// lc_Kv_Kv1_norm = lc_Kv_Kv1/lc_Kv_Kv1_low
// lc_Kv_Kv1_norm_low = lc_Kv_Kv1_low/lc_Kv_Kv1_low
// lc_Kv_Kv1_norm_high = lc_Kv_Kv1_high/lc_Kv_Kv1_low
vShift_na_def = 8
vShift_na = vShift_na_def
// vShift_na_low = -24
// vShift_na_high = 24
// vShift_na_norm_def = vShift_na_def/vShift_na_low
// vShift_na_norm = vShift_na/vShift_na_low
// vShift_na_norm_low = vShift_na_low/vShift_na_low
// vShift_na_norm_high = vShift_na_high/vShift_na_low
vShift_nais_def = 10
vShift_nais = vShift_nais_def
// vShift_nais_low = -24
// vShift_nais_high = 24
// vShift_nais_norm_def = vShift_nais_def/vShift_nais_low
// vShift_nais_norm = vShift_nais/vShift_nais_low
// vShift_nais_norm_low = vShift_nais_low/vShift_nais_low
// vShift_nais_norm_high = vShift_nais_high/vShift_nais_low
vShift_nax_def = 10
vShift_nax = vShift_nax_def
// vShift_nax_low = -24
// vShift_nax_high = 24
// vShift_nax_norm_def = vShift_nax_def/vShift_nax_low
// vShift_nax_norm = vShift_nax/vShift_nax_low
// vShift_nax_norm_low = vShift_nax_low/vShift_nax_low
// vShift_nax_norm_high = vShift_nax_high/vShift_nax_low
vShift_inact_na_def = 10
vShift_inact_na = vShift_inact_na_def
// vShift_inact_na_low = -24
// vShift_inact_na_high = 24
// vShift_inact_na_norm_def = vShift_inact_na_def/vShift_inact_na_low
// vShift_inact_na_norm = vShift_inact_na/vShift_inact_na_low
// vShift_inact_na_norm_low = vShift_inact_na_low/vShift_inact_na_low
// vShift_inact_na_norm_high = vShift_inact_na_high/vShift_inact_na_low
vShift_inact_nais_def = 15
vShift_inact_nais = vShift_inact_nais_def
// vShift_inact_nais_low = -24
// vShift_inact_nais_high = 24
// vShift_inact_nais_norm_def = vShift_inact_nais_def/vShift_inact_nais_low
// vShift_inact_nais_norm = vShift_inact_nais/vShift_inact_nais_low
// vShift_inact_nais_norm_low = vShift_inact_nais_low/vShift_inact_nais_low
// vShift_inact_nais_norm_high = vShift_inact_nais_high/vShift_inact_nais_low
vShift_inact_nax_def = 10
vShift_inact_nax = vShift_inact_nax_def
// vShift_inact_nax_low = -24
// vShift_inact_nax_high = 24
// vShift_inact_nax_norm_def = vShift_inact_nax_def/vShift_inact_nax_low
// vShift_inact_nax_norm = vShift_inact_nax/vShift_inact_nax_low
// vShift_inact_nax_norm_low = vShift_inact_nax_low/vShift_inact_nax_low
// vShift_inact_nax_norm_high = vShift_inact_nax_high/vShift_inact_nax_low
vShift_kv1ax_def = 10
vShift_kv1ax = vShift_kv1ax_def
// vShift_kv1ax_low = -24
// vShift_kv1ax_high = 24
// vShift_kv1ax_norm_def = vShift_kv1ax_def/vShift_kv1ax_low
// vShift_kv1ax_norm = vShift_kv1ax/vShift_kv1ax_low
// vShift_kv1ax_norm_low = vShift_kv1ax_low/vShift_kv1ax_low
// vShift_kv1ax_norm_high = vShift_kv1ax_high/vShift_kv1ax_low
vShift_inact_kv1ax_def = -15
vShift_inact_kv1ax = vShift_inact_kv1ax_def
// vShift_inact_kv1ax_low = -24
// vShift_inact_kv1ax_high = 24
// vShift_inact_kv1ax_norm_def = vShift_inact_kv1ax_def/vShift_inact_kv1ax_low
// vShift_inact_kv1ax_norm = vShift_inact_kv1ax/vShift_inact_kv1ax_low
// vShift_inact_kv1ax_norm_low = vShift_inact_kv1ax_low/vShift_inact_kv1ax_low
// vShift_inact_kv1ax_norm_high = vShift_inact_kv1ax_high/vShift_inact_kv1ax_low
// preAIS_border_percentage (prior to large rise in Na and K channel expression) determined according to
// Battefeld et al. (2014), Hamada and Kole (2015), and Hamada et al. (2016). Midpoint percentage
// (midpoint of sigmoid) for AIS distributions of Na based on Battefeld et al. (2014),
// similar to Hallerman et al. (2012). Kv1 according to Kole and Stuart (2012), similar to Hallerman et al.
// (2012). Kv7, Battefeld et al. (2014).
preAIS_border_percentage = 0.1
Nais_midpoint_percentage = 0.3
Kv1_ais_midpoint_percentage = 0.4
Kv7_ais_midpoint_percentage = 0.5
// For AIS sigmoidal distributions (see setparam distions())
proc defAISpts() {
total_ais_length = 0
forsec AIS total_ais_length += getdist(secname(), 0, secname(), 1)
preAIS_border = preAIS_border_percentage * total_ais_length
Nais_midpoint = Nais_midpoint_percentage * total_ais_length
Kv1_ais_midpoint = Kv1_ais_midpoint_percentage * total_ais_length
Kv7_ais_midpoint = Kv7_ais_midpoint_percentage * total_ais_length
}
defAISpts()
// ---------------------------------------------------------------------------------
// ------------------------------doargs---------------------------------------------
// Decide whether a parameter should be a fit variable (in a given simulation type)
if (mode == 1) {
Ri_doarg = 0
rpa_doarg = 0
parafact_doarg = 0
Rm_doarg = 0
Rmy_doarg = 0
Cm_doarg = 0
Cmy_doarg = 0
Cpip_doarg = 0
RmN_doarg = 0
RmA_doarg = 0
RmI_doarg = 0
RiA_doarg = 0
per_int_doarg = 0
exp_doarg = 0
}
Na_de_doarg = 1
Na_so_doarg = 1
Na_prox_doarg = 1
Na_ais_doarg = 1
Na_int_doarg = 1
Na_nod_doarg = 1
Na_end_doarg = 1
Na_col_doarg = 1
Nap_ais_doarg = 1
Nap_int_doarg = 1
Nap_nod_doarg = 1
Nap_end_doarg = 1
Kv1_de_doarg = 1
Kv1_so_doarg = 1
Kv1_prox_doarg = 1
Kv1_ais_doarg = 1
Kv1_int_doarg = 1
Kv1_nod_doarg = 1
Kv1_end_doarg = 1
Kv1_col_doarg = 1
Kv_de_doarg = 1
Kv_so_doarg = 1
Kv7_de_doarg = 1
Kv7_so_doarg = 1
Kv7_prox_doarg = 1
Kv7_ais_doarg = 1
Kv7_int_doarg = 1
Kv7_nod_doarg = 1
Kv7_end_doarg = 1
Kv7_col_doarg = 1
KCa_doarg = 1
// KCa_de_doarg = 1
// KCa_so_doarg = 1
// KCa_ais_doarg = 1
// KCa_int_doarg = 1
// KCa_nod_doarg = 1
// KCa_end_doarg = 1
// KCa_col_doarg = 1
Ca_doarg = 1
// Ca_de_doarg = 1
// Ca_so_doarg = 1
// Ca_ais_doarg = 1
// Ca_int_doarg = 1
// Ca_nod_doarg = 1
// Ca_end_doarg = 1
// Ca_col_doarg = 1
It2_doarg = 1
// It2_de_doarg = 1
// It2_so_doarg = 1
// It2_ais_doarg = 1
// It2_int_doarg = 1
// It2_nod_doarg = 1
// It2_end_doarg = 1
// It2_col_doarg = 1
H_so_doarg = 1
H_ax_doarg = 1
// maxdist_Na_apic_doarg = 0
// maxdist_Na_bas_doarg = 0
// lc_Kv_Kv1_doarg = 0
// vShift_na_doarg = 0
// vShift_nais_doarg = 0
// vShift_nax_doarg = 0
// vShift_inact_na_doarg = 0
// vShift_inact_nais_doarg = 0
// vShift_inact_nax_doarg = 0
// vShift_kv1ax_doarg = 0
// vShift_inact_kv1ax_doarg = 0
miscparam_opt = 0
// if (miscparam_opt) {
// maxdist_Na_apic_doarg = 1
// maxdist_Na_bas_doarg = 1
// lc_Kv_Kv1_doarg = 1
// }
// ---------------------------------------------------------------------------------
// ------------------------------uselogs---------------------------------------------
// uselog refers to whether a parameter will be optimized in logspace.
Na_de_uselog = 1
Na_so_uselog = 1
Na_prox_uselog = 1
Na_ais_uselog = 1
Na_int_uselog = 1
Na_nod_uselog = 1
Na_end_uselog = 1
Na_col_uselog = 1
Nap_ais_uselog = 1
Nap_int_uselog = 1
Nap_nod_uselog = 1
Nap_end_uselog = 1
Kv1_de_uselog = 1
Kv1_so_uselog = 1
Kv1_prox_uselog = 1
Kv1_ais_uselog = 1
Kv1_int_uselog = 1
Kv1_nod_uselog = 1
Kv1_end_uselog = 1
Kv1_col_uselog = 1
Kv_de_uselog = 1
Kv_so_uselog = 1
Kv7_de_uselog = 1
Kv7_so_uselog = 1
Kv7_prox_uselog = 1
Kv7_ais_uselog = 1
Kv7_int_uselog = 1
Kv7_nod_uselog = 1
Kv7_end_uselog = 1
Kv7_col_uselog = 1
KCa_uselog = 1
// KCa_de_uselog = 1
// KCa_so_uselog = 1
// KCa_ais_uselog = 1
// KCa_int_uselog = 1
// KCa_nod_uselog = 1
// KCa_end_uselog = 1
// KCa_col_uselog = 1
Ca_uselog = 1
// Ca_de_uselog = 1
// Ca_so_uselog = 1
// Ca_ais_uselog = 1
// Ca_int_uselog = 1
// Ca_nod_uselog = 1
// Ca_end_uselog = 1
// Ca_col_uselog = 1
It2_uselog = 1
// It2_de_uselog = 1
// It2_so_uselog = 1
// It2_ais_uselog = 1
// It2_int_uselog = 1
// It2_nod_uselog = 1
// It2_end_uselog = 1
// It2_col_uselog = 1
H_so_uselog = 1
H_ax_uselog = 1
// vShift_na_uselog = 0
// vShift_nais_uselog = 0
// vShift_nax_uselog = 0
// vShift_inact_na_uselog = 0
// vShift_inact_nais_uselog = 0
// vShift_inact_nax_uselog = 0
// vShift_kv1ax_uselog = 0
// vShift_inact_kv1ax_uselog = 0
// maxdist_Na_apic_uselog = 1
// maxdist_Na_bas_uselog = 1
// lc_Kv_Kv1_uselog = 1
// ---------------------------------------------------------------------------------
// --------------------------Simulation order---------------------------------------
// For determining integration method. default is 0. 1 and 2 also available.
// Check NEURON documentation for details.
order = 0
// ---------------------------------------------------------------------------------
// ----------------------------initperint-------------------------------------------
proc initperint() {local nint, k
nint = crintlist()
for k = 1, nint {
sprint(tempstr, "%s%d%s", "Rmy_", k, "_def = Rmy_def")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, " = Rmy")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_low = Rmy_low")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_high = Rmy_high")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_norm_def = Rmy_norm_def")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_norm = Rmy_norm")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_low_norm = Rmy_low_norm")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_high_norm = Rmy_high_norm")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_doarg = 1")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Rmy_", k, "_uselog = 1")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_def = Cmy_def")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, " = Cmy")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_low = Cmy_low")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_high = Cmy_high")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_norm_def = Cmy_norm_def")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_norm = Cmy_norm")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_low_norm = Cmy_low_norm")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_high_norm = Cmy_high_norm")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_doarg = 1")
execute(tempstr)
sprint(tempstr, "%s%d%s", "Cmy_", k, "_uselog = 1")
execute(tempstr)
}
tempstr = ""
}
// ---------------------------------------------------------------------------------
if (per_int_doarg) initperint()
// ---------------------------------------------------------------------------------