Cable cells¶

Warning

The interface for building and modifying cable cell objects has changed significantly; some of the documentation below is out of date.

Cable cells, which use the cell_kind cable, represent morphologically-detailed neurons as 1-d trees, with electrical and biophysical properties mapped onto those trees.

A single cell is represented by an object of type cable_cell. Properties shared by all cable cells, as returned by the recipe get_global_properties method, are described by an object of type cable_cell_global_properties.

The `cable_cell` object¶

Cable cells are constructed from a morphology and, optionally, a label_dict that associates names with particular points (locset objects) or subsets (region objects) of the morphology.

Morphologies are constructed from a segment_tree, but can also be generated via the stitch_builder, which offers a slightly higher level interface. Details are described in Constructing cell morphologies.

Each cell has particular values for its electrical and ionic properties. These are determined first by the set of global defaults, then the defaults associated with the cell, and finally by any values specified explicitly for a given subsection of the morphology via the paint method (see Electrical properties and ion values and Overriding properties locally).

Ion channels and other distributed dynamical processes are also specified on the cell via the paint method; while synapses, current clamps, gap junction locations, and the site for testing the threshold potential are specified via the place method. See Cell dynamics, below.

Constructing cell morphologies¶

Todo

TODO: Description of segment trees is in the works.

The stitch-builder interface¶

Like the segment tree, the stich_builder class constructs morphologies through attaching simple components described by a pair of mpoint values, proximal and distal. These components are mstitch objects, and they differ from segments in two regards:

Stitches are identified by a unique string identifier, in addition to an optional tag value.
Stitches can be attached to a parent stitch at either end, or anywhere in the middle.

The ability to attach a stitch some way along another stitch dictates that one stitch may correspond to more than one morphological segment once the morphology is fully specified. When these attachment points are internal to a stitch, the corresponding geometrical point is determined by linearly interpolating between the proximal and distal points.

The required header file is arbor/morph/stitch.hpp.

mstitch has two constructors:

mstitch::mstitch(std::string id, mpoint prox, mpoint dist, int tag = 0)
mstitch::mstitch(std::string id, mpoint dist, int tag = 0)

If the proximal point is omitted, it will be inferred from the point at which the stitch is attached to its parent.

The stitch_builder class collects the stitches with the add method:

stitch_builder::add(mstitch, const std::string& parent_id, double along = 1.)
stitch_builder::add(mstitch, double along = 1.)

The first stitch will have no parent. If no parent id is specified for a subsequent stitch, the last stitch added will be used as parent. The along parameter must lie between zero and one inclusive, and determines the point of attachment as a relative position between the parent’s proximal and distal points.

A stitched_morphology is constructed from a stitch_builder, and provides both the morphology built from the stitches, and methods for querying the extent of individual stitches.

class stitched_morphology¶

stitched_morphology(const stitch_builder&)¶

stitched_morphology(stitch_builder&&)¶

Construct from a stitch_builder. Note that constructing from an rvalue is more efficient, as it avoids making a copy of the underlying tree structure.

arb::morphology morphology() const¶

Return the constructed morphology object.

region stitch(const std::string &id) const¶

Return the region expression corresponding to the specified stitch.

std::vector<msize_t> segments(const std::string &id) const¶

Return the collection of segments by index comprising the specified stitch.

label_dict labels(const std::string &prefix = "") const¶

Provide a label_dict with a region entry for each stitch; if a prefix is provided, this prefix is applied to each segment id to determine the region labels.

Example code, constructing a cable cell from a T-shaped morphology specified by two stitches:

using namespace arb;

mpoint soma0{0, 0, 0, 10};
mpoint soma1{20, 0, 0, 10};
mpoint dend_end{10, 100, 0, 1};

stitch_builder builder;
builder.add({"soma", soma0, soma1, 1});
builder.add({"dend", dend_end, 4}, "soma", 0.5);

stitched_morphology stitched(std::move(builder));
cable_cell cell(stitched.morphology(), stitched.labels());

cell.paint("\"soma\"", "hh");

Identifying sites and subsets of the morphology¶

Todo

TODO: Region and locset documentation is under development.

Cell dynamics¶

Each segment in a cell may have attached to it one or more density mechanisms, which describe biophysical processes. These are processes that are distributed in space, but whose behaviour is defined purely by the state of the cell and the process at any given point.

Cells may also have point mechanisms, describing the dynamics at post-synaptic sites.

A third type of mechanism, which describes ionic reversal potential behaviour, can be specified for cells or the whole model via cell parameter settings, described below.

Mechanisms are described by a mechanism_desc object. These specify the name of the mechanism (used to find the mechanism in the mechanism catalogue) and parameter values for the mechanism that apply within a segment. A mechanism_desc is effectively a wrapper around a name and a dictionary of parameter/value settings.

Mechanism descriptions can be constructed implicitly from the mechanism name, and mechanism parameter values then set with the set method. Relevant mechanism_desc methods:

mechanism_desc::mechanism_desc(std::string name)¶: Construct a mechanism description for the mechanism named name.

mechanism_desc &mechanism_desc::set(const std::string &key, double value)¶: Sets the parameter associated with key in the description. Returns a reference to the mechanism description, so that calls to set can be chained in a single expression.

Density mechanisms are associated with a cable cell object with:

void cable_cell::paint(const region&, mechanism_desc)¶

Point mechanisms, which are associated with connection end points on a cable cell, are attached to a cell with:

void cable_cell::place(const locset&, mechanism_desc)¶

Todo

TODO: describe other place-able things: current clamps, gap junction sites, threshold potential measurement point.

Electrical properties and ion values¶

On each cell segment, electrical and ion properties can be specified by the parameters field, of type cable_cell_local_parameter_set.

The cable_cell_local_parameter_set has the following members, where an empty optional value or missing map key indicates that the corresponding value should be taken from the cell or global parameter set.

class cable_cell_local_parameter_set¶

std::unordered_map<std::string, cable_cell_ion_data> ion_data¶

The keys of this map are names of ions, whose parameters will be locally overridden. The struct cable_cell_ion_data has three fields: init_int_concentration, init_ext_concentration, and init_reversal_potential.

Internal and external concentrations are given in millimolars, i.e. mol/m³. Reversal potential is given in millivolts.

util::optional<double> init_membrane_potential¶

Initial membrane potential in millivolts.

util::optional<double> temperature_K¶

Local temperature in Kelvin.

util::optional<double> axial_resistivity¶

Local resistivity of the intracellular medium, in ohm-centimetres.

util::optional<double> membrane_capacitance¶

Local areal capacitance of the cell membrane, in Farads per square metre.

util::optional<cv_policy> discretisation¶

Method by which CV boundaries are determined when the cell is discretised. See Discretisation and CV policies.

Default parameters for a cell are given by the default_parameters field in the cable_cell object. This is a value of type cable_cell_parameter_set, which extends cable_cell_local_parameter_set by adding an additional field describing reversal potential computation:

class cable_cell_parameter_set : public cable_cell_local_parameter_set ¶

std::unordered_map<std::string, mechanism_desc> reversal_potential_method¶

Maps the name of an ion to a ‘reversal potential’ mechanism that describes how it should be computed. When no mechanism is provided for an ionic reversal potential, the reversal potential will be kept at its initial value.

Default parameters for all cells are supplied in the cable_cell_global_properties struct.

Global properties¶

class cable_cell_global_properties¶

const mechanism_catalogue *catalogue¶

all mechanism names refer to mechanism instances in this mechanism catalogue. by default, this is set to point to global_default_catalogue(), the catalogue that contains all mechanisms bundled with arbor.

double membrane_voltage_limit_mv¶

if non-zero, check to see if the membrane voltage ever exceeds this value in magnitude during the course of a simulation. if so, throw an exception and abort the simulation.

bool coalesce_synapses¶

when synapse dynamics are sufficiently simple, the states of synapses within the same discretised element can be combined for better performance. this is true by default.

std::unordered_map<std::string, int> ion_species¶

every ion species used by cable cells in the simulation must have an entry in this map, which takes an ion name to its charge, expressed as a multiple of the elementary charge. by default, it is set to include sodium “na” with charge 1, calcium “ca” with charge 2, and potassium “k” with charge 1.

cable_cell_parameter_set default_parameters¶

the default electrical and physical properties associated with each cable cell, unless overridden locally. in the global properties, every optional field must be given a value, and every ion must have its default values set in default_parameters.ion_data.

add_ion(const std::string &ion_name, int charge, double init_iconc, double init_econc, double init_revpot)¶

convenience function for adding a new ion to the global ion_species table, and setting up its default values in the ion_data table.

add_ion(const std::string &ion_name, int charge, double init_iconc, double init_econc, mechanism_desc revpot_mechanism)¶

As above, but set the initial reversal potential to zero, and use the given mechanism for reversal potential calculation.

For convenience, neuron_parameter_defaults is a predefined cable_cell_local_parameter_set value that holds values that correspond to NEURON defaults. To use these values, assign them to the default_parameters field of the global properties object returned in the recipe.

Reversal potential dynamics¶

If no reversal potential mechanism is specified for an ion species, the initial reversal potential values are maintained for the course of a simulation. Otherwise, a provided mechanism does the work, but it subject to some strict restrictions. A reversal potential mechanism described in NMODL:

May not maintain any STATE variables.
Can only write to the “eX” value associated with an ion.
Can not given as a POINT mechanism.

Essentially, reversal potential mechanisms must be pure functions of cellular and ionic state.

If a reversal potential mechanism writes to multiple ions, then if the mechanism is given for one of the ions in the global or per-cell parameters, it must be given for all of them.

Arbor’s default catalogue includes a “nernst” reversal potential, which is parameterized over a single ion, and so can be assigned to e.g. calcium in the global parameters via

cable_cell_global_properties gprop;
// ...
gprop.default_parameters.reversal_potential_method["ca"] = "nernst/ca";

This mechanism has global scalar parameters for the gas constant R and Faraday constant F, corresponding to the exact values given by the 2019 redefinition of the SI base units. These values can be changed in a derived mechanism in order to use, for example, older values of these physical constants.

mechanism_catalogue mycat(global_default_catalogue());
mycat.derive("nernst1998", "nernst", {{"R", 8.314472}, {"F", 96485.3415}});

gprop.catalogue = &mycat;
gprop.default_parameters.reversal_potential_method["ca"] = "nernst1998/ca";

Overriding properties locally¶

Todo

TODO: using paint to specify electrical properties on subsections of the morphology.

Cable cell probes¶

Various properties of a a cable cell can be sampled via one of the cable cell specific probe address described below. They fall into two classes: scalar probes are associated with a single real value, such as a membrane voltage or mechanism state value at a particular location; vector probes return multiple values corresponding to a quantity sampled over a whole cell.

The sample data associated with a cable cell probe will either be a double for scalar probes, or a cable_sample_range describing a half-open range of double values:

using cable_sample_range = std::pair<const double*, const double*>

The probe metadata passed to the sampler will be a const pointer to:

mlocation for most scalar probes;
cable_probe_point_info for point mechanism state queries;
mcable_list for most vector queries;
std::vector<cable_probe_point_info> for cell-wide point mechanism state queries.

The type cable_probe_point_info holds metadata for a single target on a cell:

struct cable_probe_point_info {
    // Target number of point process instance on cell.
    cell_lid_type target;

    // Number of combined instances at this site.
    unsigned multiplicity;

    // Point on cell morphology where instance is placed.
    mlocation loc;
};

Note that the multiplicity will always be 1 if synapse coalescing is disabled.

Cable cell probes that contingently do not correspond to a valid measurable quantity are ignored: samplers attached to them will receive no values. Mechanism state queries however will throw a cable_cell_error exception at simulation initialization if the requested state variable does not exist on the mechanism.

Cable cell probe addresses that are described by a locset may generate more than one concrete probe: there will be one per location in the locset that is satisfiable. Sampler callback functions can distinguish between different probes with the same address and id by examining their index and/or probe-specific metadata found in the probe_metadata parameter.

Membrane voltage¶

struct cable_probe_membrane_voltage {
    locset locations;
};

Queries cell membrane potential at each site in locations.

Sample value: double. Membrane potential in millivolts.
Metadata: mlocation. Location of probe.

struct cable_probe_membrane_voltage_cell {};

Queries cell membrane potential across whole cell.

Sample value: cable_sample_range. Each value is the average membrane potential in millivolts across an unbranched component of the cell, as determined by the discretisation.
Metadata: mcable_list. Each cable in the cable list describes the unbranched component for the corresponding sample value.

Axial current¶

struct cable_probe_axial_current {
    locset locations;
};

Estimate intracellular current at each site in locations, in the distal direction.

Sample value: double. Current in nanoamperes.
Metadata: mlocation. Location as of probe.

Transmembrane current¶

struct cable_probe_ion_current_density {
    locset locations;
    std::string ion;
};

Membrane current density attributed to a particular ion at each site in locations.

Sample value: double. Current density in amperes per square metre.
Metadata: mlocation. Location of probe.

struct cable_probe_ion_current_cell {
    std::string ion;
};

Membrane current attributed to a particular ion across components of the cell.

Sample value: cable_sample_range. Each value is the current in nanoamperes across an unbranched component of the cell, as determined by the discretisation.
Metadata: mcable_list. Each cable in the cable list describes the unbranched component for the corresponding sample value.

struct cable_probe_total_ion_current_density {
    locset locations;
};

Membrane current density at given locations _excluding_ capacitive currents.

Sample value: double. Current density in amperes per square metre.
Metadata: mlocation. Location of probe.

struct cable_probe_total_ion_current_cell {};

Membrane current _excluding_ capacitive currents across components of the cell.

Sample value: cable_sample_range. Each value is the current in nanoamperes across an unbranched component of the cell, as determined by the discretisation.
Metadata: mcable_list. Each cable in the cable list describes the unbranched component for the corresponding sample value.

struct cable_probe_total_current_cell {};

Total membrance current across components of the cell.

Sample value: cable_sample_range. Each value is the current in nanoamperes across an unbranched component of the cell, as determined by the discretisation.
Metadata: mcable_list. Each cable in the cable list describes the unbranched component for the corresponding sample value.

Ion concentration¶

struct cable_probe_ion_int_concentration {
    locset locations;
    std::string ion;
};

Ionic internal concentration of ion at each site in locations.

Sample value: double. Ion concentration in millimoles per litre.
Metadata: mlocation. Location of probe.

struct cable_probe_ion_int_concentration_cell {
    std::string ion;
};

Ionic external concentration of ion across components of the cell.

Sample value: cable_sample_range. Each value is the concentration in millimoles per lire across an unbranched component of the cell, as determined by the discretisation.
Metadata: mcable_list. Each cable in the cable list describes the unbranched component for the corresponding sample value.

struct cable_probe_ion_ext_concentration {
    mlocation location;
    std::string ion;
};

Ionic external concentration of ion at each site in locations.

Sample value: double. Ion concentration in millimoles per litre.
Metadata: mlocation. Location of probe.

struct cable_probe_ion_ext_concentration_cell {
    std::string ion;
};

Ionic external concentration of ion across components of the cell.

Sample value: cable_sample_range. Each value is the concentration in millimoles per lire across an unbranched component of the cell, as determined by the discretisation.
Metadata: mcable_list. Each cable in the cable list describes the unbranched component for the corresponding sample value.

Mechanism state¶

struct cable_probe_density_state {
    locset locations;
    std::string mechanism;
    std::string state;
};

Value of state variable in a density mechanism in each site in locations. If the mechanism is not defined at a particular site, that site is ignored.

Sample value: double. State variable value.
Metadata: mlocation. Location as given in the probe address.

struct cable_probe_density_state_cell {
    std::string mechanism;
    std::string state;
};

Value of state variable in a density mechanism across components of the cell.

Sample value: cable_sample_range. State variable values from the mechanism across unbranched components of the cell, as determined by the discretisation and mechanism extent.
Metadata: mcable_list. Each cable in the cable list describes the unbranched component for the corresponding sample value.

struct cable_probe_point_state {
    cell_lid_type target;
    std::string mechanism;
    std::string state;
};

Value of state variable in a point mechanism associated with the given target. If the mechanism is not associated with this target, the probe is ignored.

Sample value: double. State variable value.
Metadata: cable_probe_point_info. Target number, multiplicity and location.

struct cable_probe_point_state_cell {
    std::string mechanism;
    std::string state;
};

Value of state variable in a point mechanism for each of the targets in the cell with which it is associated.

Sample value: cable_sample_range. State variable values at each associated target.
Metadata: std::vector<cable_probe_point_info>. Target metadata for each associated target.

Discretisation and CV policies¶

For the purpose of simulation, cable cells are decomposed into discrete subcomponents called control volumes (CVs) The CVs are uniquely determined by a set of B of mlocation boundary points. For each non-terminal point h in B, there is a CV comprising the points {x: h ≤ x and ¬∃ y ∈ B s.t h < y < x}, where < and ≤ refer to the geometrical partial order of locations on the morphology. A fork point is owned by a CV if and only if all of its corresponding representative locations are in the CV.

The set of boundary points used by the simulator is determined by a CV policy. These are objects of type cv_policy, which has the following public methods:

class cv_policy¶

locset cv_boundary_points(const cable_cell&) const¶

Return a locset describing the boundary points for CVs on the given cell.

region domain() const¶

Give the subset of a cell morphology on which this policy has been declared, as a morphological region expression.

Specific CV policy objects are created by functions described below (strictly speaking, these are class constructors for classes are implicit converted to cv_policy objects). These all take a region parameter that restrict the domain of applicability of that policy; this facility is useful for specifying differing discretisations on different parts of a cell morphology. When a CV policy is constrained in this manner, the boundary of the domain will always constitute part of the CV boundary point set.

CV policies can be combined with + and | operators. For two policies A and B, A + B is a policy which gives boundary points from both A and B, while A | B is a policy which gives all the boundary points from B together with those from A which do not within the domain of B. The domain of A + B and A | B is the union of the domains of A and B.

`cv_policy_single`¶

cv_policy_single(region domain = reg::all())

Use one CV for the whole cell, or one for each connected component of the supplied domain.

`cv_policy_explicit`¶

cv_policy_explicit(locset locs, region domain = reg::all())

Use the points given by locs for CV boundaries, optionally restricted to the supplied domain.

`cv_policy_every_sample`¶

cv_policy_every_sample(region domain = reg::all())

Use every sample point in the morphology definition as a CV boundary, optionally restricted to the supplied domain. Each fork point in the domain is represented by a trivial CV.

`cv_policy_fixed_per_branch`¶

cv_policy_fixed_per_branch(unsigned cv_per_branch, region domain, cv_policy_flag::value flags = cv_policy_flag::none);

cv_policy_fixed_per_branch(unsigned cv_per_branch, cv_policy_flag::value flags = cv_policy_flag::none):

For each branch in each connected component of the domain (or the whole cell, if no domain is given), evenly distribute boundary points along the branch so as to produce exactly cv_per_branch CVs.

By default, CVs will terminate at branch ends. If the flag cv_policy_flag::interior_forks is given, fork points will be included in non-trivial, branched CVs and CVs covering terminal points in the morphology will be half-sized.

`cv_policy_max_extent`¶

cv_policy_max_extent(double max_extent, region domain, cv_policy_flag::value flags = cv_policy_flag::none);

cv_policy_max_extent(double max_extent, cv_policy_flag::value flags = cv_policy_flag::none):

As for cv_policy_fixed_per_branch, save that the number of CVs on any given branch will be chosen to be the smallest number that ensures no CV will have an extent on the branch longer than max_extent micrometres.

Cable cells¶

The cable_cell object¶

Constructing cell morphologies¶

The stitch-builder interface¶

Identifying sites and subsets of the morphology¶

Cell dynamics¶

Electrical properties and ion values¶

Global properties¶

Reversal potential dynamics¶

Overriding properties locally¶

Cable cell probes¶

Membrane voltage¶

Axial current¶

Transmembrane current¶

Ion concentration¶

Mechanism state¶

Discretisation and CV policies¶

cv_policy_single¶

cv_policy_explicit¶

cv_policy_every_sample¶

cv_policy_fixed_per_branch¶

cv_policy_max_extent¶

The `cable_cell` object¶

`cv_policy_single`¶

`cv_policy_explicit`¶

`cv_policy_every_sample`¶

`cv_policy_fixed_per_branch`¶

`cv_policy_max_extent`¶