Definition of the elements needed for specifying electrophysiological cellular mechanisms. Voltage/concentration dependent channels can be specified, but also activity dependent ion concentrations (e.g. decaying calcium pools) and synaptic mechanisms. The mechanisms which can be specified by this schema can be mapped on into the scripting languages of a number of common simulation platforms, e.g. NEURON, GENESIS. This mapping can be done a number of XML based ways, but XSL mappings are included with the NeuroMLValidator code. The elements outlined below are linked together with with those in MorphML.xsd and Biophysics.xsd in the NeuroML.xsd file to make Level 2 compliant NeuroML files The root element of any ChannelML file. Note this element will only be present in a standalone ChannelML file. For files covering many levels, neuroml will be the root element Root element containing the ions used in the mechanism, the unit system of the file (as attribute), and information on channels and/or ion concentration dynamics. Normally only the ion element and one of channel_type, synapse_type or ion_concentration should be present. One or more ions which play some role in the mechanism, e.g. transmitted by the channel, alters the rate, etc. Note: deprecated since v1.7.3 Specification of a voltage or ligand gated membrane conductance mechanism Specification of a synaptic conductance, triggered by a presynaptic event Specification of how an ion concentration alters with time, e.g. calcium dynamics. This may influence other channels (e.g. Ca dependent K channels), and other mechanisms may have a contribution to the concentration of the ion specified here (e.g. a channel transmitting calcium). Unit system of all quantities. Only SI or Physiological units are allowed! Fixed value parameters which can be used in generic expressions A single parameter which can be used in generic expressions A unique name for the parameter The default value for the parameter Definition of a voltage/concentration dependent cell membrane conductance Status of the channel specification: stable, in progress, etc. Some metadata (notes, etc.) to describe the conductance. Fixed value parameters which can be used in generic expressions The specification of how the current flow etc. into the cell relates to the membrane potential difference (e.g. Ohmic relationship) Channel specification based on the Hodgkin Huxley formalism. Deprecated! Will be removed in v2.0 Channel specification based on a kinetic scheme formalism. Deprecated! Will be removed in v2.0 Optional recommended values, e.g. for size of tables, when creating an implementation of the channel mechanism on a specific simulator A unique name for the channel mechanism Is this a specification of conductance per unit area? Note: almost all channel mechanisms to far have been density mechanisms. This attribute is subject to change when use of ChannelML for single channel conductances is supported. Definition of a synaptic mechanism Status of the synapse specification: stable, in progress, etc. Some metadata (notes, etc.) to describe the synapse. Choice of electrical synapse, or a number of chemical synaptic transmission mechanism Electrical synaptic coupling as at a gap junction Synaptic conductance with rise time and decay time For example NMDA receptor synapses An extension incorporating multiple decay time courses A facilitating and depressing synaptic mechanism A synaptic mechanism implementing basic Spike Timing Dependent Plasticity based on Song and Abbott, 2001 Electrical synaptic coupling as at a gap junction. A simple model with just a parameter for the (2 way) conductance The conductance of the electrical connection A basic synaptic mechanism with a double exponential conductance time course. This mechanism maps easily on to mechanisms in both NEURON (Exp2Syn) and GENESIS (synchan) The maximum conductance of the channel The characteristic rise time of the conductance waveform The characteristic decay time of the conductance waveform V The reversal potential of the synapse, which (along with the membrane potential) will determine the current passing through the synapse when the conductance is non zero A synaptic mechanism whose conductance can be blocked by the presence of a specific species (ion/molecule). Based on the mechanism for blocking of an NMDA receptor by Mg as outlined in Gabbiani et al, 1994, Maex DeSchutter 1998 Specification for the influence of a blocking species on the conductance of a BlockingSynapse. Based on the mechanism for blocking of an NMDA receptor by Mg as outlined in Gabbiani et al, 1994, Maex DeSchutter 1998 Name of species. For ions use lowercase, e.g. mg Concentration of species. Multiplicative factor for total conductance: 1/(1 + eta * [conc] * exp(-1* gamma * V)) mM^-1 Used in multiplicative factor for total conductance: 1/(1 + eta * [conc] * exp(-1* gamma * V)) V^-1 Used in multiplicative factor for total conductance: 1/(1 + eta * [conc] * exp(-1* gamma * V)) A more complex synaptic mechanism featuring up to 4 exponential components (1 rise and 3 decay). Currently there is only an implementation of this in a NEURON mod file. Attributed added can be gmax_2, tau_decay_2, gmax_3 and tau_decay_3. The overall conductance is effectively a linear sum of 3 independent conductances, all with the same rise time and different decays. Note that the gmaxes are specific for each conductance and scaling is calculated for each individually, so the maximum total conductance (gmax + gmax_2 + gmax_3) will only be reached when tau_decay = tau_decay_2 = tau_decay_3, otherwise peaks will not overlap. Extends DoubleExponentialSynapse The maximum conductance and decay constant of the 2nd (normally slower) component of the synaptic conductance The maximum conductance and decay constant of the 3nd (normally slower) component of the synaptic conductance. Note that either both attributes or neither should be present. Unfortunately attributeGroups can't be made optional... The maximum conductance and decay constant of the 2nd (normally slower) component of the synaptic conductance. Note that either both attributes or neither should be present. Unfortunately attributeGroups can't be made optional... The maximum conductance and decay constant of the 3nd (normally slower) component of the synaptic conductance. Note that either both attributes or neither should be present. Unfortunately attributeGroups can't be made optional... A synaptic type with facilitating and depressing amplitude. Extends MultiDecaySynapse A synaptic mechanism implementing basic Spike Timing Dependent Plasticity based on Song and Abbott, 2001 Extends MultiDecaySynapse Facilitating and depressing synaptic parameters. See mapping to NEURON mod file for implementation details. A synaptic mechanism implementing basic Spike Timing Dependent Plasticity based on Song and Abbott, 2001. See mapping to NEURON mod file for implementation details. How the current through the channel depends on the conductance of the channel. Only ohmic and integrate_and_fire supported at the moment Deprecated since v1.7.3. Use attribute cond_law and gate elements below this element instead. Note: use attribute cond_law="integrate_and_fire" and no other attributes here when using this. Signifies a current which will cause the cell to behave like an integrate and fire neuron Preferred location of conc_dependence since v1.7.3. Preferred location of conc_factor since v1.7.3. Preferred location of Q10 information since v1.7.3. Preferred location of offset information since v1.7.3. Preferred way of expressing gating complexes since v1.7.3. Introduced in v1.7.3 for new format ChannelML. Specifies which type of conductance law to use: ohmic, etc. Introduced in v1.7.3 for new format ChannelML. The ion which will flow due to the conductance. Note this should be already declared in an Ion element at the beginning of the file. Introduced in v1.7.3 for new format ChannelML. Maximum conductance density of channel. Note this will normally be reset when the channel mechanism is placed on a cell, but it it useful to have a default value here. Most implementations of these channel mechanisms (e.g. a mod file) will need a value for the reversal potential for the ion which flows through the channel. However, this is a property of the cell, as opposed to the channel. For convenience though, a typical value can be used here, so a pretty self contained script can be produced, but when used in a real cell the actual value for erev must be calculated Electrical charge of the ion in question Flags whether the reversal potential can be influenced from outside the channel (value = no; default) as is normally the case (e.g. a Ca channel whose reversal potential is influenced by a decaying calcium pool), or whether the rev pot remains fixed (just for this channel) at default_erev (value = yes) Introduced in v1.7.3 for new format ChannelML. Specifies which type of conductance law to use: ohmic, etc. Current is given by membrane potential times conductance (Ohm's law) Signifies a current which will cause the cell to behave like an integrate and fire neuron. Signifies a current which will cause the cell to behave like an integrate and fire neuron. There are many ways to describe an Integrate and Fire mechanism, this one is based on the implementation in NEURON of the COBA IandF cell as described in Brette et al (2007) Voltage at which the mechanism causes the segment/cell to fire, i.e. membrane potential will be reset to v_reset Time after a spike during which the segment will be clamped to v_reset (clamping current given by i = g_refrac*(v - v_reset)) Membrane potential is reset to this after spiking Conductance during the period t_refrac after a spike, when the current due to this mechanism is given by i = g_refrac*(v - v_reset), therefore a high value for g_refrac, e.g. 100 microsiemens, will effectively clamp the cell at v_reset Signifies an ohmic relation; the current is proportional to the potential difference across the channel. Deprecated! Will be removed in v2.0 Description of the conductance including maximum conductance density and possible (voltage and/or concentration dependent) gating mechanisms Adjustments, e.g. temperature dependence, to apply to the gating mechanisms Voltage/concentration dependent gate Maximum conductance density of channel The ion which will flow due to the conductance. Note this should be already declared in an Ion element at the beginning of the file. These items ideally shouldn't be in a specification which deals with a description of the physiology of the channel. However, some channels won't be properly implemented in the scripting mechanism of given simulator using the standard mappings unless these factors are taken into account, e.g. if the rate equations change rapidly, but the default table size isn't large enough. Comment element to give explination for the implementation preferences. Having a dedicated element as opposed to a <-- comment --> allows the comment to be repeated in the script file impl. Preferences for the table of values for the rate equations, e.g. used in the TABLE statement in NMODL, or in tabchannel GENESIS objects The maximum potential from which to calculate the tables of rate values The minimum potential from which to calculate the tables of rate values The number of divisions in the table Adjustments necessary to all the rate equations, e.g temperature dependencies, voltage offsets introduced when moving between species, etc. See the XSL mappings for more information on the meaning of these adjustments. Offset introduced to alter voltage dependence of rate equations, see NEURON/GENESIS mappings for details Q10 scaling affects the tau in the rate equations. It allows rate equations determined at one temperature to be used at a different temperature. If tauExp is the experimentally measured tau, the rate at temperature T is given by tau(T) = tauExp / q10_factor ^ ((T - experimental_temp)/10). NOTE: if fixed_q10 is specified the expression will be tau(T) = tauExp / fixed_q10, and the experimental_temp can be used to check that a simulation is running at the desired temperature. The gate to which the Q10 adjustment should be applied. If this attribute is not present, assume the adjustment applies at all gates. Q10 factor if the cell is to be run at a different temp than that at which the alpha and beta were determined. Only one of fixed_q10 or q10_factor should be specified! Q10 factor if the cell is to be run at a different temp than that at which the alpha and beta were determined. Only one of fixed_q10 or q10_factor should be specified! The experimental temperature at which alpha and beta rate equations were determined were measured Definition of an ion which is involved in this channel mechanism. Note: deprecated since v1.7.3 Some metadata (notes, etc.) to describe the conductance. Simple name for the ion. Due to the conventions used in NEURON, it is usually best to use the lower case form of the chemical symbol, e.g. na, ca, k Most implementations of these channel mechanisms (e.g. a mod file) will need a value for the reversal potential for the ion which flows through the channel. However, this is a property of the cell, as opposed to the channel. For convenience though, a typical value can be used here, so a pretty self contained script can be produced, but when used in a real cell the actual value for erev must be calculated Electrical charge of the ion in question What role the ion plays in the dynamics of the channel/cell mechanism Role ion plays in cellular mechanism, e.g. ion passes through the channel (Na, K), or the concentration of the ion is a factor in the rate equations of gating, or the mechanism alters the concentration of this ion. This greatly simplifies the number of roles an ion can play in the channel, but these options cover the majority of cases currently being modelled. Note: the term subtance is used as this formalism can also be used for other chemicals which may be transmitted, modulate channels, etc. Ion passes through the channel, e.g. Na ions permeate through an "Na Channel" WARNING: Ion passes through the channel, but the reversal potential of the ion isn't altered. This case is to cope with existing models which (rightly or wrongly) have calcium channels which lead to a calcium current, but which have a fixed reversal potential (Traub et. al 2003 CaL, Maex, De Schutter 1998 CaHVA). Be sure that this is the correct intended behaviour of the channel before using this IonRole. Concentration of ion/substance modulates dynamics/rate equations of channel, e.g. Ca dependent K channel, K permeates, but the rate is dependent on concentration of internal Ca Ion/substance is involved in internal signalling in the cell and the mechanism can alter its concentration, e.g. exponentially decaying Ca pool Preferred element for defining a gate since v1.7.3. Definition of a single voltage/concentration dependent gate, with explicit definition of open and closed states and information on the transition rates between them. For debugging/testing only! Use with caution!! Reference for the gating complex, e.g. m, h, n The number of instances of the gate, i.e. the power to which the gating variable is raised in the expression for the total conductance Closed state of a gating complex Id to use in transition elements when specifying this as the from or to state of the transition. Open state of a gating complex Id to use in transition elements when specifying this as the from or to state of the transition. The fractional conductance of the gate in this state. Has value 1 if not present Definition of a single voltage/concentration dependent gate Internal state of the gate, specifying a name, and possibly a fractional contribution. HHGate or KSGate elements will specify the rate equations, etc. for the gate, referencing this state name. The power to which the gate is raised in the expression for the total conductance Gate with Hodgkin Huxley like state transitions Gate with kinetic scheme transitions Single kinetic scheme state. Transitions will happen between these states. Deprecated! Will be removed in v2.0 Source state of the transition in kinetic scheme. Target state of the transition in kinetic scheme. Note: the following 3 attributes should always be used when using the exponential/exp_linear/sigmoidal form of expression. These are only optional here, as whole attributeGroups can't be set as optional or required. Note: the following attribute should be used when using the generic form of expression. This is optional here, as whole attributeGroups can't be set as optional or required. Transition between states in a GatingComplex Short name to use to refer to the transition, e.g. alpha, beta for forward, backward rates in HH gates Form of expression Time course of the transition between states in a GatingComplex Short name to use to refer to the time course e.g. tau Form of expression Steady state value of the transition between states in a GatingComplex Short name to use to refer to the steady state e.g. inf Form of expression Deprecated since v1.7.3. What causes the gate to open and close. A dependence on potential difference, or a voltage and (ion) concentration dependence Source state of the transition if used in kinetic scheme. Must be used with attribute target. Use this in preference to src!!! Target state of the transition if used in kinetic scheme. Must be used with attribute src Element added for *testing purposes only*. Used to "incorrectly" initialise a channel when trying to compare it to a mod file implementation (e.g. see Traub et al 2005 channels). Value here will be ignored if option in neuroConstruct "Force correct ChannelML init" is used. Use with caution!! Definition of a voltage gate. Normally this will be specified as rate equations for alpha and beta, or for tau and inf. Deprecated! Will be removed in v2.0 Definition of a mechanics of a gate which depends on voltage and concentration (e.g. Calcium conc dependent K channel). Normally this will be specified as rate equations for alpha and beta (in terms of v and conc), or for tau and inf. Deprecated! Will be removed in v2.0 Specification of the time independent scaling factor for a concentration dependent conductance. This factor will not be used n alpha, beta, etc. but the expression in expr will scale the total conductance at each time step. Name of the ion Electrical charge of the ion in question. Assumes charge of 1 if not present How the value of conductance will be expressed in the equations Expression for the time independent multiplicative factor for the concentration dependence Minimum expected concentration. May be needed by simulators (e.g. for generating tables) Maximum expected concentration. May be needed by simulators (e.g. for generating tables) Specification of the factor to use in the concentration dependence of the rate expressions of a gate Name of substance, just for reference Name of the ion Electrical charge of the ion in question. Assumes charge of 1 if not present How the value of conductance will be expressed in the rate equations Minimum expected concentration. Quite likely to be needed by simulators (e.g. for generating tables) Maximum expected concentration. Quite likely to be needed by simulators (e.g. for generating tables) alpha, beta form of rate equations. These will always be together if present. Deprecated! Will be removed in v2.0 Two more rate variables, which may be needed for calculating a non standard tau, inf, e.g. Kdr in the Purkinje cell model. tau and inf will be calculated as normal unless otherwise specified. alpha, beta form of rate equations of voltage and conc dependent channels. These will always be together if present Choice of the various rate constant expressions allowed Note: use generic as opposed to generic_equation_hh. The latter will be removed in v2.0 Note: use generic as opposed to generic_equation_hh. The latter will be removed in v2.0 Rate constant expressions allowed for voltage and conc dependent channels. Note, at this stage no Akd like expression for a generic voltage/conc dep experssion. Time will tell if there's an expression common enough across different models to be expressed in such a way Note: use generic as opposed to generic_equation_hh. The latter will be removed in v2.0 Note: use generic as opposed to generic_equation_hh. The latter will be removed in v2.0 Definition of a rate constant equation. A parameter which is used in the equation Definition of a type of rate constant equation which takes parameters A, k, d and maps to either exponential, sigmoidal or linoidal. Note: this expression is has been useful to include when the type is, e.g. linoid, to remind users of the form of the equation. However, it's use should be discouraged, as it could be assumed that changing this attribute can change the form of the equation (as for generic_equation_hh). It's better to include the form of the equation as a comment, as in the examples. This attribute may be removed in v2.0 Definition of a type of rate constant equation Note: only variable allowed in expression is v (or for an expression for tau or inf, alpha and beta can be used too). Also, liberal use of brackets, e.g. 5.0*(exp (-50*(v +46))) instead of 5.0* exp (-50*(v +46)) is advised, due to GENESIS's handling of exp, abs, etc. Specification of how an ion concentration alters with time, e.g. calcium dynamics. This may influence other channels (e.g. Ca dependent K channels), and other mechanisms may have a contribution to the concentration of the ion specified here. Status of the ion conc mech specification: stable, in progress, etc. Some metadata to describe the ion concentration Which ion is involved in mechanism. At present there is only one choice of a model for this process, more can be added later.. A unique name for this ion concentration mechanism, as opposed to name of the ion used. Which ion is involved in an ion_concentration mechanism. Note in v2.0 the attribute form for defining the name will be required. Element for parameters in a decaying pool model of ion concentration (e.g. calcium pool) Resting concentration of ion. NOTE: In v2.0 this element will be removed. Attribute resting_conc will be used instead. Exponential decay time of pool. NOTE: In v2.0 this element will be removed. Attribute decay_constant will be used instead. Reciprocal of exponential decay time constant of pool The maximum concentration which the ion pool should be allowed get to. NOTE: In v2.0 this element will be removed. Attribute ceiling will be used instead. Resting concentration of ion. NOTE: In v2.0 the option for a resting_conc element will be removed. Attribute resting_conc will be required instead. Exponential decay time of pool. Either decay_constant or inv_decay_constant must be included. NOTE: In v2.0 the option for a decay_constant/inv_decay_constant element will be removed. Attribute decay_constant/inv_decay_constant will be used instead. Reciprocal of exponential decay time of pool. Either decay_constant or inv_decay_constant must be included. NOTE: In v2.0 the option for a decay_constant/inv_decay_constant element will be removed. Attribute decay_constant/inv_decay_constant will be used instead. The maximum concentration which the ion pool should be allowed get to. NOTE: In v2.0 the option for a ceiling element will be removed. Attribute ceiling will be used instead. Information on the volume of the ion pool The volume of the pool is calculated from the thickness of the shell inside the membrane. This will have to be multiplied by the surface area of the relevant compartment. NOTE: In v2.0 the option for a shell_thickness element will be removed. Attribute shell_thickness will be used instead. The volume of the pool is calculated from the thickness of the shell inside the membrane. This will have to be multiplied by the surface area of the relevant compartment. NOTE: In v2.0 the option for a shell_thickness element will be removed. Attribute shell_thickness will be used instead. (IN PROGRESS, not stable!!!!) In this case the parameter which determines how quickly the internal pool 'fills' is given as a fixed value. Note this is a far from ideal way to express this value, but needed to be included as this was the parameter which was all that was present in a number of models, e.g. Traub et al. 2003 Layer 2/3 cell. The dC/dt will be calculated from dC/dt = - phi * Ica + [Ca]/decay_constant. See mod/GENESIS impl for more details Generic parameter used in rate equations Enumeration of core equation types, used from v1.7.3: exp_linear, sigmoidal, exponential Of the form: A * exp((v-V1/2)/B) Of the form: A / (1 + exp((v-V1/2)/B)) Of the form: A * ((v-V1/2)/B) / (1 - exp(-((v-V1/2)/B))) A generic expression for the rates. etc. in the expr attribute. If possible the expression should be fit into one of the standard forms above (e.g. exponential, etc.) Core equation types prior to v1.7.3, linoidal, sigmoidal, exponential Of the form: A * exp(k * (v-d)) Of the form: A / (1 + exp(k * (v-d))) Of the form: A * (k * (v-d)) / (1 - exp(-(k * (v-d))))