diff --git a/docs/source/user/py/rdesigneur/rdes.rst b/docs/source/user/py/rdesigneur/rdes.rst index 7d77f8fb9f06e9b28c1119b58bd155319e54f9b8..6bfdd048677b0fdda65b33c11cb2eafdd554b7fc 100644 --- a/docs/source/user/py/rdesigneur/rdes.rst +++ b/docs/source/user/py/rdesigneur/rdes.rst @@ -1,17 +1,13 @@ -**Rdesigneur: Building multiscale models** +========================================== +Rdesigneur: Building multiscale models ========================================== -.. Upi Bhalla - -.. Aug 26 2016. Updated July 2018 - -.. -------------- - -Contents --------- +| Author: Upi Bhalla +| Date: Aug 26 2016, +| Last-Updated: July 31 2018 +| By: Upi Bhalla -.. contents:: - :depth: 3 +------------------------------ Introduction ------------ diff --git a/docs/source/user/py/rdesigneur/rdesigneur/index_rd.rst b/docs/source/user/py/rdesigneur/rdesigneur/index_rd.rst deleted file mode 100644 index a729cb8b0a2f2a9d357f566bd8821085078f7571..0000000000000000000000000000000000000000 --- a/docs/source/user/py/rdesigneur/rdesigneur/index_rd.rst +++ /dev/null @@ -1,13 +0,0 @@ -.. MOOSE documentation master file, created by - sphinx-quickstart on Tue Jul 31 19:05:47 2018. - You can adapt this file completely to your liking, but it should at least - contain the root `toctree` directive. - -Rdesignuer -=========== - -.. toctree:: - :maxdepth: 2 - - rdes - multi_rdes diff --git a/docs/source/user/py/rdesigneur/rdesigneur/multi_rdes.rst b/docs/source/user/py/rdesigneur/rdesigneur/multi_rdes.rst deleted file mode 100644 index d240f1b1cbb2412ab0d9331eff0ccb4f25d136c7..0000000000000000000000000000000000000000 --- a/docs/source/user/py/rdesigneur/rdesigneur/multi_rdes.rst +++ /dev/null @@ -1,52 +0,0 @@ -************************ -Rdesigneur Examples -************************ - -.. hidden-code-block:: reStructuredText - :label: How to run these examples - - Each of the following examples can be run by clicking on the green source button - on the right side of each example, and running from within a ``.py`` python file - on a computer where moose is installed. - - Alternatively, all the files mentioned on this page can be found in the main - moose directory. They can be found under - - (...)/moose/moose-examples/snippets - - They can be run by typing - - $ python filename.py - - in your command line, where filename.py is the python file you want to run. - - All of the following examples show one or more methods within each python file. - For example, in the ``cubeMeshSigNeur`` section, there are two blue tabs - describing the ``cubeMeshSigNeur.createSquid()`` and ``cubeMeshSigNeur.main()`` - methods. - - The filename is the bit that comes before the ``.`` in the blue boxes, with - ``.py`` added at the end of it. In this case, the file name would be - ``cubeMeshSigNeur.py``. -| - -Building Chemical-Electrical Signalling Models ----------------------------------------------- - -Building a compartment -^^^^^^^^^^^^^^^^^^^^^^ - -.. automodule:: testRdesigneur - :members: - -Inserting Spines and viewing -^^^^^^^^^^^^^^^^^^^^^^^^^^^^ - -.. automodule:: insertSpines - :members: - -Proceeding with Spines -^^^^^^^^^^^^^^^^^^^^^^ - -.. automodule:: testWigglySpines - :members: diff --git a/docs/source/user/py/rdesigneur/rdesigneur/rdes.rst b/docs/source/user/py/rdesigneur/rdesigneur/rdes.rst deleted file mode 100644 index 161ff2f97e15771e76ca1d6f81315e8eb3ca4743..0000000000000000000000000000000000000000 --- a/docs/source/user/py/rdesigneur/rdesigneur/rdes.rst +++ /dev/null @@ -1,1964 +0,0 @@ -========================================== -Rdesigneur: Building multiscale models -========================================== - -| Author: Upi Bhalla -| Date: Aug 26 2016, -| Last-Updated: July 31 2018 -| By: Upi Bhalla - ------------------------------- - -Contents --------- - -.. contents:: - :depth: 3 - -Introduction ------------- - -**Rdesigneur** (Reaction Diffusion and Electrical SIGnaling in NEURons) -is an interface to the multiscale modeling capabilities in MOOSE. It is -designed to build models incorporating biochemical signaling pathways in -dendrites and spines, coupled to electrical events in neurons. -Rdesigneur assembles models from predefined parts: it delegates the -details to specialized model definition formats. Rdesigneur combines one -or more of the following cell parts to build models: - -- Neuronal morphology -- Dendritic spines -- Ion channels -- Reaction systems -- Adaptors that couple between these for multiscale models - -It also folds in simulation input and output - -- Time-series stimuli for molecular concentration change and reaction rates -- Current and voltage clamp -- Synaptic input. -- Time-series plots -- File dumps -- 3-D neuronal graphics - -Rdesigneur's main role is to specify how these are put together, -including assigning parameters for the model. Using Rdesigneur one can compactly -and quickly put together quite complex multiscale models. - -Quick Start ------------ - -Here we provide a few use cases, building up from a minimal model to a -reasonably complete multiscale model spanning chemical and electrical -signaling. The files for these examples are also available in -``moose-examples/tutorials/Rdesigneur``, and the file names are mentioned -as we go along. - -Bare Rdesigneur: single passive compartment -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex1_minimalModel.py* - -If we don't provide any arguments at all to the Rdesigneur, it makes a -model with a single passive electrical compartment in the MOOSE path -``/model/elec/soma``. Here is how to do this: - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur() - rdes.buildModel() - -To confirm that it has made a compartment with some default values we -can add a line: - -:: - - moose.showfields( rdes.soma ) - -This should produce the output: - -:: - - [ /model[0]/elec[0]/soma[0] ] - diameter = 0.0005 - fieldIndex = 0 - Ra = 7639437.26841 - y0 = 0.0 - Rm = 424413.177334 - index = 0 - numData = 1 - inject = 0.0 - initVm = -0.065 - Em = -0.0544 - y = 0.0 - numField = 1 - path = /model[0]/elec[0]/soma[0] - dt = 0.0 - tick = -2 - z0 = 0.0 - name = soma - Cm = 7.85398163398e-09 - x0 = 0.0 - Vm = -0.06 - className = ZombieCompartment - idValue = 465 - length = 0.0005 - Im = 1.3194689277e-08 - x = 0.0005 - z = 0.0 - -Simulate and display current pulse to soma -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex2.0_currentPulse.py* - -A more useful script would run and display the model. Rdesigneur can -help with the stimulus and the plotting. This simulation has the same -passive compartment, and current is injected as the simulation runs. -This script displays the membrane potential of the soma as it charges -and discharges. - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur( - stimList = [['soma', '1', '.', 'inject', '(t>0.1 && t<0.2) * 2e-8']], - plotList = [['soma', '1', '.', 'Vm', 'Soma membrane potential']], - ) - rdes.buildModel() - moose.reinit() - moose.start( 0.3 ) - rdes.display() - -The *stimList* defines a stimulus. Each entry has five arguments: - -:: - - `[region_in_cell, region_expression, moose_object, parameter, expression_string]` - -- ``region_in_cell`` specifies the objects to stimulate. Here it is - just the soma. -- ``region_expression`` specifies a geometry based calculation to - decide whether to apply the stimulus. The value must be >0 for the - stimulus to be present. Here it is just 1. ``moose_object`` specifies - the simulation object to operate upon during the stimulus. Here the - ``.`` means that it is the soma itself. In other models it might be a - channel on the soma, or a synapse, and so on. -- ``parameter`` specifies the simulation parameter on the moose object - that the stimulus will modify. Here it is the injection current to - the soma compartment. -- ``expression_string`` calculates the value of the parameter, - typically as a function of time. Here we use the function - ``(t>0.1 && t<0.2) * 2e-8`` which evaluates as 2e-8 between the times - of 0.1 and 0.2 seconds. - -To summarise this, the *stimList* here means *inject a current of 20nA -to the soma between the times of 0.1 and 0.2 s*. - -The *plotList* defines what to plot. It has a similar set of arguments: - -:: - - `[region_in_cell, region_expression, moose_object, parameter, title_of_plot]` - -These mean the same thing as for the stimList except for the title of -the plot. - -The *rdes.display()* function causes the plots to be displayed. - -.. figure:: ../../../../images/rdes2_passive_squid.png - :alt: Plot for current input to passive compartment - - Plot for current input to passive compartment - -When we run this we see an initial depolarization as the soma settles -from its initial -65 mV to a resting Em = -54.4 mV. These are the -original HH values, see the example above. At t = 0.1 seconds there is -another depolarization due to the current injection, and at t = 0.2 -seconds this goes back to the resting potential. - -Simulate and display voltage clamp stimulus to soma -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex2.1_vclamp.py* - -This model introduces the voltage clamp stimulus on a passive compartment. -As before, we add a few lines to define the stimulus and plot. -This script displays both the membrane potential, and the holding current -of the voltage clamp circuit as -it charges and discharges the passive compartment model. - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur( - stimList = [['soma', '1', '.', 'vclamp', '-0.065 + (t>0.1 && t<0.2) * 0.02' ]], - plotList = [ - ['soma', '1', '.', 'Vm', 'Soma membrane potential'], - ['soma', '1', 'vclamp', 'current', 'Soma holding current'], - ] - ) - rdes.buildModel() - moose.reinit() - moose.start( 0.3 ) - rdes.display() - -Here the *stimList* line tells the system to deliver a voltage clamp (vclamp) -on the soma, starting at -65 mV and jumping up by 20 mV between 0.1 and 0.2 -seconds. The *plotList* now includes two entries, and will generate two plots. -The first is for plotting the soma membrane potential, just to be sure that -the voltage clamp is doing its job. - -.. figure:: ../../../../images/ex2.1_vclamp_a.png - :alt: Plot for membrane potential in voltage clamp - - Plot for membrane potential in voltage clamp - -The second graph plots the holding current. Note the capacitive transients. - -.. figure:: ../../../../images/ex2.1_vclamp_b.png - :alt: Plot for holding current for voltage clamp - - Plot for holding current for voltage clamp - -HH Squid model in a single compartment -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex3.0_squid_currentPulse.py* - -Here we put the Hodgkin-Huxley squid model channels into a passive -compartment. The HH channels are predefined as prototype channels for -Rdesigneur, - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - chanProto = [['make_HH_Na()', 'Na'], ['make_HH_K()', 'K']], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '1200' ], - ['K', 'soma', 'Gbar', '360' ]], - stimList = [['soma', '1', '.', 'inject', '(t>0.1 && t<0.2) * 1e-8' ]], - plotList = [['soma', '1', '.', 'Vm', 'Membrane potential']] - ) - - rdes.buildModel() - moose.reinit() - moose.start( 0.3 ) - rdes.display() - -Here we introduce two new model specification lines: - -- **chanProto**: This specifies which ion channels will be used in the - model. Each entry here has two fields: the source of the channel - definition, and (optionally) the name of the channel. In this example - we specify two channels, an Na and a K channel using the original - Hodgkin-Huxley parameters. As the source of the channel definition we - use the name of the Python function that builds the channel. The - *make\_HH\_Na()* and *make\_HH\_K()* functions are predefined but we - can also specify our own functions for making prototypes. We could - also have specified the channel prototype using the name of a channel - definition file in ChannelML (a subset of NeuroML) format. -- **chanDistrib**: This specifies *where* the channels should be placed - over the geometry of the cell. Each entry in the chanDistrib list - specifies the distribution of parameters for one channel using four - entries: - - ``[object_name, region_in_cell, parameter, expression_string]`` - - In this case the job is almost trivial, since we just have a single - compartment named *soma*. So the line - - ``['Na', 'soma', 'Gbar', '1200' ]`` - - means *Put the Na channel in the soma, and set its maximal - conductance density (Gbar) to 1200 Siemens/m^2*. - -As before we apply a somatic current pulse. Since we now have HH -channels in the model, this generates action potentials. - -.. figure:: ../../../../images/rdes3_squid.png - :alt: Plot for HH squid simulation - - Plot for HH squid simulation - -There are several interesting things to do with the model by varying stimulus -parameters: - - - Change injection current. - - Put in a protocol to get rebound action potential. - - Put in a current ramp, and run it for a different duration - - Put in a frequency chirp, and see how the squid model is tuned - to a certain frequency range. - - Modify channel or passive parameters. See if it still fires. - - Try the frequency chirp on the cell with parameters changed. Does - the tuning change? - - -HH Squid model with voltage clamp -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex3.1_squid_vclamp.py* - -This is the same squid model, but now we add a voltage clamp to the squid -and monitor the holding current. This stimulus line is identical to ex2.1. - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - chanProto = [['make_HH_Na()', 'Na'], ['make_HH_K()', 'K']], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '1200' ], - ['K', 'soma', 'Gbar', '360' ]], - stimList = [['soma', '1', '.', 'vclamp', '-0.065 + (t>0.1 && t<0.2) * 0.02' ]], - plotList = [ - ['soma', '1', '.', 'Vm', 'Membrane potential'], - ['soma', '1', 'vclamp', 'current', 'Soma holding current'] - ] - ) - rdes.buildModel() - moose.reinit() - moose.start( 0.3 ) - rdes.display() - -Here we see the classic HH current response, a downward brief deflection due to -the Na channel, and a slower upward sustained current due to the K delayed -rectifier. - -.. figure:: ../../../../images/ex3.1_squid_vclamp.png - :alt: Plot for HH squid voltage clamp pulse. - - Plot for HH squid voltage clamp pulse. - -Here are some suggestions for further exploration: - - - Monitor individual channel currents through additional plots. - - Convert this into a voltage clamp series. Easiest way to do this is - to complete the rdes.BuildModel, then delete the Function object - on the */model/elec/soma/vclamp*. Now you can simply set the 'command' - field of the vclamp in a for loop, going from -ve to +ve voltages. - Remember, SI units. You may wish to capture the plot vectors each - cycle. The plot vectors are accessed by something like - - ``moose.element( '/model/graphs/plot1' ).vector`` - - -HH Squid model in an axon -~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex3.2_squid_axon_propgn.py* - -Here we put the Hodgkin-Huxley squid model into a long compartment that -is subdivided into many segments, so that we can watch action potentials -propagate. Most of this example is boilerplate code to build a spiral -axon. There is a short *rdesigneur* segment that takes the spiral axon -prototype and populates it with channels, and sets up the display. Later -examples will show you how to read morphology files to specify the -neuronal geometry. - -:: - - import numpy as np - import moose - import pylab - import rdesigneur as rd - - numAxonSegments = 200 - comptLen = 10e-6 - comptDia = 1e-6 - RM = 1.0 - RA = 10.0 - CM = 0.01 - - def makeAxonProto(): - axon = moose.Neuron( '/library/axon' ) - prev = rd.buildCompt( axon, 'soma', RM = RM, RA = RA, CM = CM, dia = 10e-6, x=0, dx=comptLen) - theta = 0 - x = comptLen - y = 0.0 - - for i in range( numAxonSegments ): - dx = comptLen * np.cos( theta ) - dy = comptLen * np.sin( theta ) - r = np.sqrt( x * x + y * y ) - theta += comptLen / r - compt = rd.buildCompt( axon, 'axon' + str(i), RM = RM, RA = RA, CM = CM, x = x, y = y, dx = dx, dy = dy, dia = comptDia ) - moose.connect( prev, 'axial', compt, 'raxial' ) - prev = compt - x += dx - y += dy - - return axon - - moose.Neutral( '/library' ) - makeAxonProto() - - rdes = rd.rdesigneur( - chanProto = [['make_HH_Na()', 'Na'], ['make_HH_K()', 'K']], - cellProto = [['elec','axon']], - chanDistrib = [ - ['Na', '#', 'Gbar', '1200' ], - ['K', '#', 'Gbar', '360' ]], - stimList = [['soma', '1', '.', 'inject', '(t>0.01 && t<0.2) * 2e-11' ]], - plotList = [['soma', '1', '.', 'Vm', 'Membrane potential']], - moogList = [['#', '1', '.', 'Vm', 'Vm (mV)']] - ) - - rdes.buildModel() - moose.reinit() - - rdes.displayMoogli( 0.00005, 0.05, 0.0 ) - -.. figure:: ../../../../images/ex3.2_axon_propagating_AP.png - :alt: Axon with propagating action potential - - Axon with propagating action potential - -Note how we explicitly create the prototype axon on '/library', and then -specify it using the *cellProto* line in the rdesigneur. The moogList -specifies the 3-D display. See below for how to set up and use these -displays. - -Action potential collision in HH Squid axon model -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex3.3_AP_collision.py* - -This is identical to the previous example, except that now we deliver current -injection at at two points, the soma and a point along the axon. The modified -stimulus line is: - -:: - - ... - stimList = [['soma', '1', '.', 'inject', '(t>0.01 && t<0.2) * 2e-11' ], - ['axon100', '1', '.', 'inject', '(t>0.01 && t<0.2) * 3e-11' ]], - ... - -Watch how the AP is triggered bidirectionally from the stimulus point on the -100th segment of the axon, and observe what happens when two action potentials -bump into each other. - -.. figure:: ../../../../images/ex3.3_AP_collision.png - :alt: Colliding action potentials - - Colliding action potentials - - - -HH Squid model in a myelinated axon -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex3.4_myelinated_axon.py* - -This is a curious cross-species chimera model, where we embed the HH -equations into a myelinated example model. As for the regular axon -above, most of the example is boilerplate setup code. Note how we -restrict the HH channels to the nodes of Ranvier using a conditional -test for the diameter of the axon segment. - -:: - - import numpy as np - import moose - import pylab - import rdesigneur as rd - - numAxonSegments = 405 - nodeSpacing = 100 - comptLen = 10e-6 - comptDia = 2e-6 # 2x usual - RM = 100.0 # 10x usual - RA = 5.0 - CM = 0.001 # 0.1x usual - - nodeDia = 1e-6 - nodeRM = 1.0 - nodeCM = 0.01 - - def makeAxonProto(): - axon = moose.Neuron( '/library/axon' ) - x = 0.0 - y = 0.0 - prev = rd.buildCompt( axon, 'soma', RM = RM, RA = RA, CM = CM, dia = 10e-6, x=0, dx=comptLen) - theta = 0 - x = comptLen - - for i in range( numAxonSegments ): - r = comptLen - dx = comptLen * np.cos( theta ) - dy = comptLen * np.sin( theta ) - r = np.sqrt( x * x + y * y ) - theta += comptLen / r - if i % nodeSpacing == 0: - compt = rd.buildCompt( axon, 'axon' + str(i), RM = nodeRM, RA = RA, CM = nodeCM, x = x, y = y, dx = dx, dy = dy, dia = nodeDia ) - else: - compt = rd.buildCompt( axon, 'axon' + str(i), RM = RM, RA = RA, CM = CM, x = x, y = y, dx = dx, dy = dy, dia = comptDia ) - moose.connect( prev, 'axial', compt, 'raxial' ) - prev = compt - x += dx - y += dy - - return axon - - moose.Neutral( '/library' ) - makeAxonProto() - - rdes = rd.rdesigneur( - chanProto = [['make_HH_Na()', 'Na'], ['make_HH_K()', 'K']], - cellProto = [['elec','axon']], - chanDistrib = [ - ['Na', '#', 'Gbar', '12000 * (dia < 1.5e-6)' ], - ['K', '#', 'Gbar', '3600 * (dia < 1.5e-6)' ]], - stimList = [['soma', '1', '.', 'inject', '(t>0.01 && t<0.2) * 1e-10' ]], - plotList = [['soma,axon100,axon200,axon300,axon400', '1', '.', 'Vm', 'Membrane potential']], - moogList = [['#', '1', '.', 'Vm', 'Vm (mV)']] - ) - - rdes.buildModel() - - for i in moose.wildcardFind( "/model/elec/#/Na" ): - print i.parent.name, i.Gbar - - moose.reinit() - - rdes.displayMoogli( 0.00005, 0.05, 0.0 ) - -When you run the example, keep an eye out for a few things: - -- **saltatory conduction:** This is the way the action potential jumps - from one node of Ranvier to the next. Between the nodes it is just - passive propagation. -- **Failure to propagate:** Observe that the second and fourth action - potentials fails to trigger propagation along the axon. Here we have - specially tuned the model properties so that this happens. With a - larger RA of 10.0, the model will be more reliable. -- **Speed:** Compare the propagation speed with the previous, - unmyelinated axon. Note that the current model is larger! - -.. figure:: ../../../../images/rdes3.2_myelinated_axon.png - :alt: Myelinated axon with propagating action potential - - Myelinated axon with propagating action potential - -Alternate (non-squid) way to define soma -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex4.0_scaledSoma.py* - -The default HH-squid axon is not a very convincing soma. Rdesigneur offers a -somewhat more general way to define the soma in the cell prototype line. - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - # cellProto syntax: ['somaProto', 'name', dia, length] - cellProto = [['somaProto', 'soma', 20e-6, 200e-6]], - chanProto = [['make_HH_Na()', 'Na'], ['make_HH_K()', 'K']], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '1200' ], - ['K', 'soma', 'Gbar', '360' ]], - stimList = [['soma', '1', '.', 'inject', '(t>0.01 && t<0.05) * 1e-9' ]], - plotList = [['soma', '1', '.', 'Vm', 'Membrane potential']], - moogList = [['#', '1', '.', 'Vm', 'Vm (mV)']] - ) - - rdes.buildModel() - soma = moose.element( '/model/elec/soma' ) - print( 'Soma dia = {}, length = {}'.format( soma.diameter, soma.length ) ) - moose.reinit() - - rdes.displayMoogli( 0.0005, 0.06, 0.0 ) - -Here the crucial line is the *cellProto* line. There are four arguments here: - - ``['somaProto', 'name', dia, length]`` - - - The first argument tells the system to use a prototype soma, that is - a single cylindrical compartment. - - The second argument is the name to give the cell. - - The third argument is the diameter. Note that this is a double, - not a string. - - The fourth argument is the length of the cylinder that makes up the - soma. This too is a double, not a string. - The cylinder is oriented along the x axis, with one end at (0,0,0) - and the other end at (length, 0, 0). - -This is what the soma looks like: - -.. figure:: ../../../../images/ex4.0_scaledSoma.png - :alt: Image of soma. - - Image of soma. - -It a somewhat elongated soma, being a cylinder 10 times as long as it is wide. - -Ball-and-stick model of a neuron -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex4.1_ballAndStick.py* - -A somewhat more electrically reasonable model of a neuron has a soma and a -single dendrite, which can itself be subdivided into segments so that it -can exhibit voltage gradients, have channel and receptor distributions, -and so on. This is accomplished in *rdesigneur* using a variant of the -cellProto syntax. - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - # cellProto syntax: ['ballAndStick', 'name', somaDia, somaLength, dendDia, dendLength, numDendSegments ] - # The numerical arguments are all optional - cellProto = [['ballAndStick', 'soma', 20e-6, 20e-6, 4e-6, 500e-6, 10]], - chanProto = [['make_HH_Na()', 'Na'], ['make_HH_K()', 'K']], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '1200' ], - ['K', 'soma', 'Gbar', '360' ], - ['Na', 'dend#', 'Gbar', '400' ], - ['K', 'dend#', 'Gbar', '120' ] - ], - stimList = [['soma', '1', '.', 'inject', '(t>0.01 && t<0.05) * 1e-9' ]], - plotList = [['soma', '1', '.', 'Vm', 'Membrane potential']], - moogList = [['#', '1', '.', 'Vm', 'Vm (mV)']] - ) - rdes.buildModel() - soma = moose.element( '/model/elec/soma' ) - moose.reinit() - rdes.displayMoogli( 0.0005, 0.06, 0.0 ) - -As before, the *cellProto* line plays a key role. Here, because we have a long -dendrite, we have a few more numerical arguments. All of the numerical -arguments are optional. - - ``['ballAndStick', 'name', somaDia, somaLength, dendDia, dendLength, numDendSegments ]`` - - - The first argument specifies a ballAndStick model: soma + dendrite. - The length of the dendrite is along the x axis. The soma is a single - segment, the dendrite can be more than one. - - The second argument is the name to give the cell. - - Arg 3 is the soma diameter, as a double. - - Arg 4 is the length of the soma, as a double. - - Arg 5 is the diameter of the dendrite, as a double. - - Arg 6 is the length of the dendrite, as a double. - - Arg 7 is the number of segments into which the dendrite should be - divided. This is a positive integer greater than 0. - -This is what the ball-and-stick cell looks like: - -.. figure:: ../../../../images/ex4.1_ballAndStick.png - :alt: Image of ball and stick cell. - - Image of ball and stick cell. - -In this version of the 3-D display, the soma is displayed as a bit blocky -rather than round. -Note that we have populated the dendrite with Na and K channels and it has -10 segments, so it supports action potential propagation. The snapshot -illustrates this. - -Here are some things to try: - - - Change the length of the dendrite - - Change the number of segments. Explore what it does to accuracy. How - will you know that you have an accurate model? - -Benchmarking simulation speed -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex4.2_ballAndStickSpeed.py* - -The ball-and-stick model gives us an opportunity to check out your system -and how computation scales with model size. While we're at it we'll deliver -a sine-wave stimulus just to see how it can be done. The test model is -very similar to the previous one, ex4.1: - -:: - - import moose - import pylab - import rdesigneur as rd - import time - rdes = rd.rdesigneur( - cellProto = [['ballAndStick', 'soma', 20e-6, 20e-6, 4e-6, 500e-6, 10]], - chanProto = [['make_HH_Na()', 'Na'], ['make_HH_K()', 'K']], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '1200' ], - ['K', 'soma', 'Gbar', '360' ], - ['Na', 'dend#', 'Gbar', '400' ], - ['K', 'dend#', 'Gbar', '120' ] - ], - stimList = [['soma', '1', '.', 'inject', '(1+cos(t/10))*(t>31.4 && t<94) * 0 - .2e-9' ]], - plotList = [ - ['soma', '1', '.', 'Vm', 'Membrane potential'], - ['soma', '1', '.', 'inject', 'Stimulus current'] - ], - ) - rdes.buildModel() - runtime = 100 - moose.reinit() - t0= time.time() - moose.start( runtime ) - print "Real time to run {} simulated seconds = {} seconds".format( runtime, time - .time() - t0 ) - - rdes.display() - -While the real point of this simulation is to check speed, it does illustrate -how to deliver a stimulus shaped like a sine wave: - -.. figure:: ../../../../images/ex4.2_sine_stim.png - :alt: Sine-wave shaped stimulus. - - Sine-wave shaped stimulus. - -We can see that the cell has a peculiar response to this. Not surprising, as -the cell uses HH channels which are not good at rate coding. - -.. figure:: ../../../../images/ex4.2_spiking.png - :alt: Spiking response to sine-wave shaped stimulus. - - Spiking response to sine-wave shaped stimulus. - -As a reference point, on a fast 2018 laptop this benchmark runs in 5.4 seconds. -Some more things to try for benchmarking: - - - How slow does it get if you turn on the 3-D moogli display? - - Is it costlier to run 2 compartments for 1000 seconds, or - 200 compartments for 10 seconds? - -Synaptic stimulus: random (Possion) -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex5.0_random_syn_input.py* - -In this example we introduce synaptic inputs: both the receptor channels -and a means for stimulating the channels. We do this in a passive model. - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur( - cellProto = [['somaProto', 'soma', 20e-6, 200e-6]], - chanProto = [['make_glu()', 'glu']], - chanDistrib = [['glu', 'soma', 'Gbar', '1' ]], - stimList = [['soma', '0.5', 'glu', 'randsyn', '50' ]], - # Deliver stimulus to glu synapse on soma, at mean 50 Hz Poisson. - plotList = [['soma', '1', '.', 'Vm', 'Soma membrane potential']] - ) - rdes.buildModel() - moose.reinit() - moose.start( 0.3 ) - rdes.display() - -Most of the rdesigneur setup uses familiar syntax. - -Novelty 1: we use the default built-in glutamate receptor model, in chanProto. -We just put it in the soma at a max conductance of 1 Siemen/sq metre. - -Novelty 2: We specify a new kind of stimulus in the stimList: - - ``['soma', '0.5', 'glu', 'randsyn', '50' ]`` - -Most of this is similar to previous stimLists. - - - arg0: 'soma': the named compartments in the cell to populate with - the *glu* receptor - - arg1: '0.5': Tell the system to use a uniform synaptic weight of 0.5. - This argument could be a more complicated expression incorporating - spatial arguments. Here it is just uniform. - - arg2: 'glu': Which receptor to stimulate - - arg3: 'randsyn': Apply random (Poisson) synaptic input. - - arg4: '50': Mean firing rate of the Poisson input. Note that this last - argument could be a function of time and hence is quite versatile. - -As the model has no voltage-gated channels, we do not see spiking. - -.. figure:: ../../../../images/ex5.0_random_syn_input.png - :alt: Random synaptic input with a Poisson distribution. - - Random synaptic input with a Poisson distribution. - -Things to try: Vary the rate and the weight of the synaptic input. - -Synaptic stimulus: periodic -~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex5.1_periodic_syn_input.py* - -This is almost identical to 5.0, except that the input is now perfectly -periodic. The one change is of an argument in the stimList to say -``periodicsyn`` rather than ``randsyn``. - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur( - cellProto = [['somaProto', 'soma', 20e-6, 200e-6]], - chanProto = [['make_glu()', 'glu']], - chanDistrib = [['glu', 'soma', 'Gbar', '1' ]], - - # Deliver stimulus to glu synapse on soma, periodically at 50 Hz. - stimList = [['soma', '0.5', 'glu', 'periodicsyn', '50' ]], - plotList = [['soma', '1', '.', 'Vm', 'Soma membrane potential']] - ) - rdes.buildModel() - moose.reinit() - moose.start( 0.3 ) - rdes.display() - -As designed, we get periodically firing synaptic input. - -.. figure:: ../../../../images/ex5.1_periodic_syn_input.png - :alt: Periodic synaptic input - - Periodic synaptic input - - -Reaction system in a single compartment -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex6_chem_osc.py* - -Here we use the compartment as a place in which to embed a chemical -model. The chemical oscillator model is predefined in the rdesigneur -prototypes. Its general form is: - -:: - - s ---a---> a // s goes to a, catalyzed by a. - s ---a---> b // s goes to b, catalyzed by a. - a ---b---> s // a goes to s, catalyzed by b. - b -------> s // b is degraded irreversibly to s - -Here is the script: - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - turnOffElec = True, - diffusionLength = 1e-3, # Default diffusion length is 2 microns - chemProto = [['makeChemOscillator()', 'osc']], - chemDistrib = [['osc', 'soma', 'install', '1' ]], - plotList = [['soma', '1', 'dend/a', 'conc', 'a Conc'], - ['soma', '1', 'dend/b', 'conc', 'b Conc']] - ) - rdes.buildModel() - b = moose.element( '/model/chem/dend/b' ) - b.concInit *= 5 - moose.reinit() - moose.start( 200 ) - - rdes.display() - -In this special case we set the turnOffElec flag to True, so that -Rdesigneur only sets up chemical and not electrical calculations. This -makes the calculations much faster, since we disable electrical -calculations and delink chemical calculations from them. - -We also have a line which sets the ``diffusionLength`` to 1 mm, so that -it is bigger than the 0.5 mm squid axon segment in the default -compartment. If you don't do this the system will subdivide the -compartment into the default 2 micron voxels for the purposes of putting -in a reaction-diffusion system. We discuss this case below. - -Note how the *plotList* is done here. To remind you, each entry has five -arguments - -:: - - [region_in_cell, region_expression, moose_object, parameter, title_of_plot] - -The change from the earlier usage is that the ``moose_object`` now -refers to a chemical entity, in this example the molecule *dend/a*. The -simulator builds a default chemical compartment named *dend* to hold the -reactions defined in the *chemProto*. What we do in this plot is to -select molecule *a* sitting in *dend*, and plot its concentration. Then -we do this again for molecule *b*. - -After the model is built, we add a couple of lines to change the initial -concentration of the molecular pool *b*. Note its full path within -MOOSE: */model/chem/dend/b*. It is scaled up 5x to give rise to slowly -decaying oscillations. - -.. figure:: ../../../../images/rdes4_osc.png - :alt: Plot for single-compartment reaction simulation - - Plot for single-compartment reaction simulation - -Reaction-diffusion system -~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex7.0_spatial_chem_osc.py* - -In order to see what a reaction-diffusion system looks like, we assign the -``diffusionLength`` expression in the previous example to a much shorter -length, and add a couple of lines to set up 3-D graphics for the -reaction-diffusion product: - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - turnOffElec = True, - #This subdivides the length of the soma into 2 micron voxels - diffusionLength = 2e-6, - chemProto = [['makeChemOscillator()', 'osc']], - chemDistrib = [['osc', 'soma', 'install', '1' ]], - plotList = [['soma', '1', 'dend/a', 'conc', 'Concentration of a'], - ['soma', '1', 'dend/b', 'conc', 'Concentration of b']], - moogList = [['soma', '1', 'dend/a', 'conc', 'a Conc', 0, 360 ]] - ) - - rdes.buildModel() - bv = moose.vec( '/model/chem/dend/b' ) - bv[0].concInit *= 2 - bv[-1].concInit *= 2 - moose.reinit() - - rdes.displayMoogli( 1, 400, rotation = 0, azim = np.pi/2, elev = 0.0 ) - -This is the new value for diffusion length. - -:: - - diffusionLength = 2e-3, - -With this change we tell *rdesigneur* to use the diffusion length of 2 microns. -This happens to be the default too. The 500-micron axon segment is now -subdivided into 250 voxels, each of which has a reaction system and -diffusing molecules. -To make it more picturesque, we have added a line after the plotList, to -display the outcome in 3-D: - -:: - - moogList = [['soma', '1', 'dend/a', 'conc', 'a Conc', 0, 360 ]] - -This line says: take the model compartments defined by ``soma`` as the -region to display, do so throughout the the geometry (the ``1`` -signifies this), and over this range find the chemical entity defined by -``dend/a``. For each ``a`` molecule, find the ``conc`` and dsiplay it. -There are two optional arguments, ``0`` and ``360``, which specify the -low and high value of the displayed variable. - -In order to initially break the symmetry of the system, we change the -initial concentration of molecule b at each end of the cylinder: - -:: - - bv[0].concInit *= 2 - bv[-1].concInit *= 2 - -If we didn't do this the entire system would go through a few cycles of -decaying oscillation and then reach a boring, spatially uniform, steady -state. Try putting an initial symmetry break elsewhere to see what -happens. - -To display the concenctration changes in the 3-D soma as the simulation -runs, we use the line - -:: - - rdes.displayMoogli( 1, 400, rotation = 0, azim = np.pi/2, elev = 0.0 ) - -The arguments mean: *displayMoogli( frametime, runtime, rotation, azimuth, elevation )* -Here, - -:: - - frametime = time by which simulation advances between display updates - runtime = Total simulated time - rotation = angle by which display rotates in each frame, in radians. - azimuth = Azimuth angle of view point, in radians - elevation = elevation angle of view point, in radians - -When we run this, we first get a 3-D display with the oscillating -reaction-diffusion system making its way inward from the two ends. After -the simulation ends the plots for all compartments for the whole run -come up. - -.. figure:: ../../../../images/rdes5_reacdiff.png - :alt: Display for oscillatory reaction-diffusion simulation - - Display for oscillatory reaction-diffusion simulation - -For those who would rather use the much simpler matplotlib 3-D display option, -this is what the same simulation looks like: - -.. figure:: ../../../../images/ex7.0_spatial_chem_osc.png - :alt: Display for oscillatory reac-diff simulation using matplotlib - - Display for oscillatory reac-diff simulation using matplotlib - -Primer on using the 3-D MOOGLI display -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -There are two variants of the MOOGLI display. The first, named Moogli, -uses OpenGL and OpenSceneGraph. It is fast to display, slow to load, and -difficult to compile. It produces much better looking 3-D graphics. -The second is a fallback interface using mplot3d, which is a library of -Matplotlib and so should be generally available. It is slower to display, -faster to load, but needs no special compilation. It uses stick graphics -and though it conveys much the same information, isn't as nice to look at -as the original Moogli. Its controls are more or less the same but less -smooth than the original Moogli. - -Here is a short primer on the 3-D display controls. - -- *Roll, pitch, and yaw*: Use the letters *r*, *p*, and *y*. To rotate - backwards, use capitals. -- *Zoom out and in*: Use the *,* and *.* keys, or their upper-case - equivalents, *<* and *>*. Easier to remember if you think in terms of - the upper-case. -- *Left/right/up/down*: Arrow keys. -- *Quit*: control-q or control-w. -- You can also use the mouse or trackpad to control most of the above. -- By default rdesigneur gives Moogli a small rotation each frame. It is - the *rotation* argument in the line: - - ``displayMoogli( frametime, runtime, rotation )`` - -These controls operate over and above this rotation, but the rotation -continues. If you set the rotation to zero you can, with a suitable -flick of the mouse, get the image to rotate in any direction you choose -as long as the window is updating. - -Diffusion of a single molecule -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex7.1_diffusive_gradient.py* - -This is simply a test model to confirm that simple diffusion happens as -expected. While the model is just that of a single pool, we spend a few lines -taking snapshots of the spatial profile of this pool. - -:: - - import moose - import pylab - import re - import rdesigneur as rd - import matplotlib.pyplot as plt - import numpy as np - - moose.Neutral( '/library' ) - moose.Neutral( '/library/diffn' ) - moose.CubeMesh( '/library/diffn/dend' ) - A = moose.Pool( '/library/diffn/dend/A' ) - A.diffConst = 1e-10 - - rdes = rd.rdesigneur( - turnOffElec = True, - diffusionLength = 1e-6, - chemProto = [['diffn', 'diffn']], - chemDistrib = [['diffn', 'soma', 'install', '1' ]], - moogList = [ - ['soma', '1', 'dend/A', 'conc', 'A Conc', 0, 360 ] - ] - ) - rdes.buildModel() - - rdes.displayMoogli( 1, 2, rotation = 0, azim = -np.pi/2, elev = 0.0, block = False ) - av = moose.vec( '/model/chem/dend/A' ) - for i in range(10): - av[i].concInit = 1 - moose.reinit() - plist = [] - for i in range( 20 ): - plist.append( av.conc[:200] ) - moose.start( 2 ) - fig = plt.figure( figsize = ( 10, 12 ) ) - plist = np.array( plist ).T - plt.plot( range( 0, 200 ), plist ) - plt.xlabel( "position ( microns )" ) - plt.ylabel( "concentration ( mM )" ) - plt.show( block = True ) - - -Here are the snapshots, overlaid in a single plot: - -.. figure:: ../../../../images/ex7.1_diffusive_gradient.png - :alt: Display of how a molecule A spreads through the inter - - Display for simple time-series of spread of a diffusing molecule - using matplotlib - - -Multiscale models: single compartment -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex8.0_multiscale_KA_phosph.py* - -The next few examples are for the multiscale modeling that is the main purpose -of rdesigneur and MOOSE as a whole. These are 'toy' examples in that the -chemical and electrical signaling is simplified, but they exhibit dynamics -that are of real interest. - -The first example is of a bistable system where the feedback loop comprises of - -`calcium influx -> chemical activity -> channel modulation -> electrical activity -> calcium influx.` - -Calcium enters through voltage gated calcium channels, leads to enzyme -activation and phosphorylation of a KA channel, which depolarizes the cell, -so it spikes more, so more calcium enters. - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - elecDt = 50e-6, - chemDt = 0.002, - chemPlotDt = 0.002, - # cellProto syntax: ['somaProto', 'name', dia, length] - cellProto = [['somaProto', 'soma', 12e-6, 12e-6]], - chemProto = [['./chem/chanPhosphByCaMKII.g', 'chem']], - chanProto = [ - ['make_Na()', 'Na'], - ['make_K_DR()', 'K_DR'], - ['make_K_A()', 'K_A' ], - ['make_Ca()', 'Ca' ], - ['make_Ca_conc()', 'Ca_conc' ] - ], - # Some changes to the default passive properties of the cell. - passiveDistrib = [['.', 'soma', 'CM', '0.03', 'Em', '-0.06']], - chemDistrib = [['chem', 'soma', 'install', '1' ]], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '300' ], - ['K_DR', 'soma', 'Gbar', '250' ], - ['K_A', 'soma', 'Gbar', '200' ], - ['Ca_conc', 'soma', 'tau', '0.0333' ], - ['Ca', 'soma', 'Gbar', '40' ] - ], - adaptorList = [ - [ 'dend/chan', 'conc', 'K_A', 'modulation', 0.0, 70 ], - [ 'Ca_conc', 'Ca', 'dend/Ca', 'conc', 0.00008, 2 ] - ], - # Give a + pulse from 5 to 7s, and a - pulse from 20 to 21. - stimList = [['soma', '1', '.', 'inject', '((t>5 && t<7) - (t>20 && t<21)) * 1.0e-12' ]], - plotList = [ - ['soma', '1', '.', 'Vm', 'Membrane potential'], - ['soma', '1', '.', 'inject', 'current inj'], - ['soma', '1', 'K_A', 'Ik', 'K_A current'], - ['soma', '1', 'dend/chan', 'conc', 'Unphosph K_A conc'], - ['soma', '1', 'dend/Ca', 'conc', 'Chem Ca'], - ], - ) - - rdes.buildModel() - moose.reinit() - moose.start( 30 ) - - rdes.display() - -There is only one fundamentally new element in this script: - -**adaptor List:** `[source, sourceField, dest, destField, offset, scale]` -The adaptor list maps between molecular, electrical or even structural -quantities in the simulation. At present it is linear mapping, in due course -it may evolve to an arbitrary function. - -The two adaptorLists in the above script do the following: - - ``[ 'dend/chan', 'conc', 'K_A', 'modulation', 0.0, 70 ]``: - -Use the concentration of the 'chan' molecule in the 'dend' compartment, -to modulate the conductance of the 'K_A' channel such that the basal -conductance is zero and 1 millimolar of 'chan' results in a conductance that is -70 times greater than the baseline conductance of the channel, *Gbar*. - -It is advisable to use the field *'modulation'* on channels undergoing scaling, -rather than to directly assign the conductance *'Gbar'*. This is because -*Gbar* is an absolute conductance, and therefore it is scaled to the area of -the electrical segment. This makes it difficult to keep track of. *Modulation* -is a simple multiplier term onto *Gbar*, and is therefore easier to work with. - - ``[ 'Ca_conc', 'Ca', 'dend/Ca', 'conc', 0.00008, 2 ]``: - -Use the concentration of *Ca* as computed in the electrical model, to assign -the concentration of molecule *Ca* on the dendrite compartment. There is a -basal level of 80 nanomolar, and every unit of electrical *Ca* maps to 2 -millimolar of chemical *Ca*. - -The arguments in the adaptorList are: - - * **Source and Dest**: Strings. These can be either a molecular or an - electrical object. To identify a molecular object, it should be - prefixed with the name of the chemical compartment, which is one - of *dend, spine, psd*. Thus *dend/chan* specifies a molecule - named *'chan'* sitting in the *'dend'* compartment. - - To identify an electrical object, just pass in its path, - such as '.' or *'Ca_conc'*. - - Note that the adaptors do **not** need to know anything about the - location. It is assumed that the adaptors do their job wherever - the specified source and dest coexist. There is a subtlety here - due to the different length and time scales. The rule of thumb - is that the adaptor averages whichever one is subdivided more finely. - - - Example 1: Molecules are typically spatially partitioned into - short voxels (micron-scale) compared to typical 100-micron - electrical - segments. So an adaptor going from molecules to, say, channel - conductance, would average all the molecular voxels that fit - in the electrical segment. - - Example 2: Electrical activity is typically much faster than - chemical. - So an adaptor going from an electrical entity (Ca computed from - channel opening) to molecules (Chemical Ca concentration) would - average all the time-steps between updates to the molecule. - - * **Fields**: Strings. These are simply the field names on the - objects coupled by the adaptors. - - * **offset and scale**: Doubles. At present the adaptor is just a - straight-line conversion, obeying ``y = mx + c``. The computed - output is *y*, averaged input is *x*, offset is *c* and scale is *m*. - -There is a handy new line to specify cellular passive properties: - -**passiveDistrib:** `['.', path, field, value, field, value, ... ]`, - - * '.': This is just a placeholder. - * path: String. Specifies the object whose parameters are to be changed. - * field: String. Name of the field on the object. - * value: String, that is the value has to be enclosed in quotes. The - value to be assigned to the object. - -With these in place, the model behavior is rather neat. It starts out silent, -then we apply 2 seconds of +ve current injection. - -.. figure:: ../../../../images/ex8.0_multiscale_currInj.png - :alt: Current injection stimuli for multiscale model. - - Current injection stimuli for multiscale model. - -The cell fires briskly, and keeps firing even when the current injection -drops to zero. - -.. figure:: ../../../../images/ex8.0_multiscale_cell_spiking.png - :alt: Firing responses of cell with multiscale signaling. - - Firing responses of cell with multiscale signaling. - -The firing of the neuron leads to Ca influx. - -.. figure:: ../../../../images/ex8.0_multiscale_Ca.png - :alt: Calcium buildup in cell due to firing. - - Calcium buildup in cell due to firing. - -The chemical reactions downstream of Ca lead to phosphorylation of the K_A -channel. Only the unphosphorylated K_A channel is active, so the net effect -is to reduce K_A conductance while the Ca influx persists. - -.. figure:: ../../../../images/ex8.0_multiscale_KA_conc.png - :alt: Removal of KA channel due to phosphorylation. - - Removal of KA channel due to phosphorylation. - - -Since the phosphorylated form has low conductance, the cell becomes more -excitable and keeps firing even when the current injection is stopped. It takes -a later, -ve current injection to turn the firing off again. - -Suggestions for things to do with the model: - - - Vary the adaptor settings, which couple electrical to chemical - signaling and vice versa. - - Play with the channel densities - - Open the chem model in moosegui and vary its parameters too. - -Multiscale model spanning PSD, spine head and dendrite -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex8.2_multiscale_glurR_phosph_3compt.py* - -This is another multiscale model on similar lines to 8.0. It is structurally -and computationally more complicated, because the action is distributed between -spines and dendrites, but formally it does the same thing: it turns on and -stays on after a strong stimulus, due to phosphorylation of a (receptor) -channel leading to greater excitability. - -`calcium influx -> chemical activity -> channel modulation -> electrical activity -> calcium influx.` - -The model is bistable as long as synaptic input keeps coming along at a basal -rate, in this case 1 Hz. - -Here we have two new lines, to do with addition of spines. These are discussed -in detail in a later example. For now it is enough to know that the -**spineProto** line defines one of the prototype spines to be used to put into -the model, and the **spineDistrib** line tells the system where to put them, -and how widely to space them. - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur( - elecDt = 50e-6, - chemDt = 0.002, - diffDt = 0.002, - chemPlotDt = 0.02, - useGssa = False, - # cellProto syntax: ['ballAndStick', 'name', somaDia, somaLength, dendDia, d - endLength, numDendSegments ] - cellProto = [['ballAndStick', 'soma', 12e-6, 12e-6, 4e-6, 100e-6, 2 ]], - chemProto = [['./chem/chanPhosph3compt.g', 'chem']], - spineProto = [['makeActiveSpine()', 'spine']], - chanProto = [ - ['make_Na()', 'Na'], - ['make_K_DR()', 'K_DR'], - ['make_K_A()', 'K_A' ], - ['make_Ca()', 'Ca' ], - ['make_Ca_conc()', 'Ca_conc' ] - ], - passiveDistrib = [['.', 'soma', 'CM', '0.01', 'Em', '-0.06']], - spineDistrib = [['spine', '#dend#', '50e-6', '1e-6']], - chemDistrib = [['chem', '#', 'install', '1' ]], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '300' ], - ['K_DR', 'soma', 'Gbar', '250' ], - ['K_A', 'soma', 'Gbar', '200' ], - ['Ca_conc', 'soma', 'tau', '0.0333' ], - ['Ca', 'soma', 'Gbar', '40' ] - ], - adaptorList = [ - [ 'psd/chan_p', 'n', 'glu', 'modulation', 0.1, 1.0 ], - [ 'Ca_conc', 'Ca', 'spine/Ca', 'conc', 0.00008, 8 ] - ], - # Syn input basline 1 Hz, and 40Hz burst for 1 sec at t=20. Syn weight - # is 0.5, specified in 2nd argument as a special case stimLists. - stimList = [['head#', '0.5','glu', 'periodicsyn', '1 + 40*(t>10 && t<11)']], - plotList = [ - ['soma', '1', '.', 'Vm', 'Membrane potential'], - ['#', '1', 'spine/Ca', 'conc', 'Ca in Spine'], - ['#', '1', 'dend/DEND/Ca', 'conc', 'Ca in Dend'], - ['#', '1', 'spine/Ca_CaM', 'conc', 'Ca_CaM'], - ['head#', '1', 'psd/chan_p', 'conc', 'Phosph gluR'], - ['head#', '1', 'psd/Ca_CaM_CaMKII', 'conc', 'Active CaMKII'], - ] - ) - moose.seed(123) - rdes.buildModel() - moose.reinit() - moose.start( 25 ) - rdes.display() - - -This is how it works: - -This is a ball-and-stick model with a couple of spines sitting on the dendrite. -The spines get synaptic input onto NMDARs and gluRs. There is a baseline -input rate of 1 Hz thoughout, and there is a burst at 40 Hz for 1 second at -t = 10s. - -.. figure:: ../../../../images/ex8.2_Vm.png - :alt: Membrane potential responses of cell with synaptic input and multiscale signaling - - Membrane potential responses of cell with synaptic input and multiscale signaling - - -At baseline, we just have small EPSPs and little Ca influx. A burst of -strong synaptic input causes Ca entry into the spine via NMDAR. - -.. figure:: ../../../../images/ex8.2_Ca_spine.png - :alt: Calcium influx into spine. - - Calcium influx into spine. - -Ca diffuses from the spine into the dendrite and spreads. In the graph below -we see how Calcium goes into the 50-odd voxels of the dendrite. - -.. figure:: ../../../../images/ex8.2_Ca_dend.png - :alt: Calcium influx and diffusion in dendrite. - - Calcium influx and diffusion in dendrite. - - -The Ca influx into the spine -triggers activation of CaMKII and its translocation to the PSD, where -it phosphorylates and increases the conductance of gluR. We have two spines -with slightly different geometry, so the CaMKII activity differs slightly. - -.. figure:: ../../../../images/ex8.2_active_CaMKII.png - :alt: Activation of CaMKII and translocation to PSD - - Activation of CaMKII and translocation to PSD - - -Now that gluR has a greater weight, the baseline synaptic input keeps -Ca trickling in enough to keep the CaMKII active. - -Here are the reactions: - -:: - - Ca+CaM <===> Ca_CaM; Ca_CaM + CaMKII <===> Ca_CaM_CaMKII (all in - spine head, except that the Ca_CaM_CaMKII translocates to the PSD) - - chan ------Ca_CaM_CaMKII-----> chan_p; chan_p ------> chan (all in PSD) - -Suggestions: - - - Add GABAR using make_GABA(), put it on soma or dendrite. Stimulate it - after 20 s to see if you can turn off the sustained activation - - Replace the 'periodicsyn' in stimList with 'randsyn'. This gives - Poisson activity at the specified mean frequency. Does the switch - remain reliable? - - What are the limits of various parameters for this switching? You - could try basal synaptic rate, burst rate, the various scaling factors - for the adaptors, the densities of various channels, synaptic weight, - and so on. - - In real life an individual synaptic EPSP is tiny, under a millivolt. - How many synapses would you need to achieve this kind of switching? - You can play with # of synapses by altering the spacing between - spines as the third argument of spineDistrib. - -Multiscale model in which spine geometry changes due to signaling -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex8.3_spine_vol_change.py* - -This model is very similar to 8.2. The main design difference is that -*adaptor*, instead of just modulating the gluR conductance, scales the -entire spine cross-section area, with all sorts of electrical and chemical -ramifications. There are a lot of plots, to illustrate some of these outcomes. - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur( - elecDt = 50e-6, - chemDt = 0.002, - diffDt = 0.002, - chemPlotDt = 0.02, - useGssa = False, - stealCellFromLibrary = True, # Simply move library model to use for sim - cellProto = [['ballAndStick', 'soma', 12e-6, 12e-6, 4e-6, 100e-6, 2 ]], - chemProto = [['./chem/chanPhosph3compt.g', 'chem']], - spineProto = [['makeActiveSpine()', 'spine']], - chanProto = [ - ['make_Na()', 'Na'], - ['make_K_DR()', 'K_DR'], - ['make_K_A()', 'K_A' ], - ['make_Ca()', 'Ca' ], - ['make_Ca_conc()', 'Ca_conc' ] - ], - passiveDistrib = [['.', 'soma', 'CM', '0.01', 'Em', '-0.06']], - spineDistrib = [['spine', '#dend#', '50e-6', '1e-6']], - chemDistrib = [['chem', '#', 'install', '1' ]], - chanDistrib = [ - ['Na', 'soma', 'Gbar', '300' ], - ['K_DR', 'soma', 'Gbar', '250' ], - ['K_A', 'soma', 'Gbar', '200' ], - ['Ca_conc', 'soma', 'tau', '0.0333' ], - ['Ca', 'soma', 'Gbar', '40' ] - ], - adaptorList = [ - # This scales the psdArea of the spine by # of chan_p. Note that - # the cross-section area of the spine head is identical to psdArea. - [ 'psd/chan_p', 'n', 'spine', 'psdArea', 0.1e-12, 0.01e-12 ], - [ 'Ca_conc', 'Ca', 'spine/Ca', 'conc', 0.00008, 8 ] - ], - # Syn input basline 1 Hz, and 40Hz burst for 1 sec at t=20. Syn wt=10 - stimList = [['head#', '10','glu', 'periodicsyn', '1 + 40*(t>10 && t<11)']], - plotList = [ - ['soma', '1', '.', 'Vm', 'Membrane potential'], - ['#', '1', 'spine/Ca', 'conc', 'Ca in Spine'], - ['#', '1', 'dend/DEND/Ca', 'conc', 'Ca in Dend'], - ['head#', '1', 'psd/chan_p', 'n', 'Amount of Phospho-chan'], - ['head#', '1', 'spine/CaMKII', 'conc', 'Conc of CaMKII in spine'], - ['head#', '1', '.', 'Cm', 'Capacitance of spine head'], - ['head#', '1', '.', 'Rm', 'Membrane res of spine head'], - ['head#', '1', '.', 'Ra', 'Axial res of spine head'], - ['head#', '1', 'glu', 'Gbar', 'Conductance of gluR'], - ['head#', '1', 'NMDA', 'Gbar', 'Conductance of NMDAR'], - ] - ) - moose.seed(123) - rdes.buildModel() - moose.reinit() - moose.start( 25 ) - rdes.display() - - -The key *adaptor* line is as follows: - -``[ 'psd/chan_p', 'n', 'spine', 'psdArea', 0.1e-12, 0.01e-12 ]`` - -Here, we use the phosphorylated *chan_p* molecule in the PSD as a proxy for -processes that control spine size. We operate on a special object called -*spine* which manages many aspects of spines in the model (see below). Here -we control the *psdArea*, which defines the cross-section area of the spine -head and by extension of the PSD too. We keep a minimum spine area of 0.1 um^2, -and a scaling factor of 0.01um^2 per phosphorylated molecule. - -The reaction system is identical to the one in *ex8.2*: - -:: - - Ca+CaM <===> Ca_CaM; Ca_CaM + CaMKII <===> Ca_CaM_CaMKII (all in - spine head, except that the Ca_CaM_CaMKII translocates to the PSD) - - chan ------Ca_CaM_CaMKII-----> chan_p; chan_p ------> chan (all in PSD) - -Rather than list all the 10 plots, here are a few to show what is going on. - -First, just the spiking activity of the cell. Here the burst of activity is -followed by a few seconds of enhanced synaptic weight, followed by subthreshold -EPSPs: - -.. figure:: ../../../../images/ex8.3_Vm.png - :alt: Membrane potential and spiking. - - Membrane potential and spiking. - -Then, we fast-forward to the amount of *chan_p* which is the molecule that -controls spine size scaling: - -.. figure:: ../../../../images/ex8.3_chan_p.png - :alt: Molecule that controles spine size - - Molecule that controles spine size - -This causes some obvious outcomes. One of them is to increase the synaptic -conductance of the glutamate receptor. The system assumes that the conductance -of all channels in the PSD scales linearly with the psdArea. - -.. figure:: ../../../../images/ex8.3_gluR.png - :alt: Conductance of glutamate receptor - - Conductance of glutamate receptor - -Here is one of several non-intuitive outcomes. Because the spine volume has -increased, the concentration of molecules in the spine is diluted out. So -the concentration of active CaMKII actually falls when the spine gets bigger. -In a more detailed model, this would be a race between the increase in spine -size and the time taken for diffusion and further reactions to replenish -CaMKII. In the current model we don't have a diffusive coupling of CaMKII to -the dendrite, so this replenishment doesn't happen. - -.. figure:: ../../../../images/ex8.3_CaMKII_spine.png - :alt: Concentration of CaMKII in the spine - - Concentration of CaMKII in the spine - -In the simulation we display several other electrical and chemical properties -that change with spine size. The diffusion properties also change since the -cross-section areas are altered. This is harder to visualize but has large -effects on coupling to the dendrite, -especially if the *shaftDiameter* is the parameter scaled by the signaling. - - -Suggestions: - - - The Spine class (instance: spine) manages several possible scaling - targets on the spine geometry: shaftLength, shaftDiameter, - headLength, headDiameter, psdArea, headVolume, totalLength. Try them - out. Think about mechanisms by which molecular concentrations might - affect each. - - When volume changes, we assume that the molecular numbers stay - fixed, so concentration changes. Except for buffered molecules, where - we assume concentration remains fixed. Use this to design a bistable - simply relying on molecules and spine geometry terms. - - Even more interesting, use it to design an oscillator. You could look - at Bhalla, BiophysJ 2011 for some ideas. - - - -Morphology: Load .swc morphology file and view it -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex9.0_load_neuronal_morphology_file.py* - -Here we build a passive model using a morphology file in the .swc file -format (as used by NeuroMorpho.org). The morphology file is predefined -for Rdesigneur and resides in the directory ``./cells``. We apply a -somatic current pulse, and view the somatic membrane potential in a -plot, as before. To make things interesting we display the morphology in -3-D upon which we represent the membrane potential as colors. - -:: - - import sys - import moose - import rdesigneur as rd - - if len( sys.argv ) > 1: - fname = sys.argv[1] - else: - fname = './cells/h10.CNG.swc' - rdes = rd.rdesigneur( - cellProto = [[fname, 'elec']], - stimList = [['soma', '1', '.', 'inject', 't * 25e-9' ]], - plotList = [['#', '1', '.', 'Vm', 'Membrane potential'], - ['#', '1', 'Ca_conc', 'Ca', 'Ca conc (uM)']], - moogList = [['#', '1', '.', 'Vm', 'Soma potential']] - ) - rdes.buildModel() - moose.reinit() - rdes.displayMoogli( 0.001, 0.1, rotation = 0.02 ) - - -Here the new concept is the cellProto line, which loads in the specified -cell model: - -:: - - `[ filename, cellname ]` - -The system recognizes the filename extension and builds a model from the -swc file. It uses the cellname **elec** in this example. - -We use a similar line as in the reaction-diffusion example, to build up -a Moogli display of the cell model: - -:: - - `moogList = [['#', '1', '.', 'Vm', 'Soma potential']]` - -Here we have: - -:: - - # : the path to use for selecting the compartments to display. - This wildcard means use all compartments. - 1 : The expression to use for the compartments. Again, `1` means use - all of them. - . : Which object in the compartment to display. Here we are using the - compartment itself, so it is just a dot. - Vm : Field to display - Soma potential : Title for display. - -.. figure:: ../../../../images/ex9.0_passive_cell_morpho.png - :alt: 3-D display for passive neuron - - 3-D display for passive neuron - -Suggestions: - - - The tutorial directory already has a number of pre-loaded files from - NeuroMorpho. Pass them in to ex9.0 on the command line: - - `python ex9.0_load_neuronal_morphology_file.py <morpho.swc>` - - Grab other morphology files from NeuroMorpho.org, try them out. - -Build an active neuron model by putting channels into a morphology file -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex9.1_chans_in_neuronal_morph.py* - -Here we load in a morphology file and distribute voltage-gated ion channels -over the neuron. The voltage-gated channels are obtained from a -number of channelML files, located in the ``./channels`` subdirectory. -Since we have a spatially extended neuron, we need to specify the -spatial distribution of channel densities too. - -:: - - import moose - import rdesigneur as rd - rdes = rd.rdesigneur( - chanProto = [ - ['./chans/hd.xml'], - ['./chans/kap.xml'], - ['./chans/kad.xml'], - ['./chans/kdr.xml'], - ['./chans/na3.xml'], - ['./chans/nax.xml'], - ['./chans/CaConc.xml'], - ['./chans/Ca.xml'] - ], - cellProto = [['./cells/h10.CNG.swc', 'elec']], - chanDistrib = [ \ - ["hd", "#dend#,#apical#", "Gbar", "50e-2*(1+(p*3e4))" ], - ["kdr", "#", "Gbar", "p < 50e-6 ? 500 : 100" ], - ["na3", "#soma#,#dend#,#apical#", "Gbar", "850" ], - ["nax", "#soma#,#axon#", "Gbar", "1250" ], - ["kap", "#axon#,#soma#", "Gbar", "300" ], - ["kap", "#dend#,#apical#", "Gbar", - "300*(H(100-p*1e6)) * (1+(p*1e4))" ], - ["Ca_conc", "#", "tau", "0.0133" ], - ["kad", "#soma#,#dend#,#apical#", "Gbar", "50" ], - ["Ca", "#", "Gbar", "50" ] - ], - stimList = [['soma', '1', '.', 'inject', '(t>0.02) * 1e-9' ]], - plotList = [['#', '1', '.', 'Vm', 'Membrane potential'], - ['#', '1', 'Ca_conc', 'Ca', 'Ca conc (uM)']], - moogList = [['#', '1', 'Ca_conc', 'Ca', 'Calcium conc (uM)', 0, 120], - ['#', '1', '.', 'Vm', 'Soma potential']] - ) - - rdes.buildModel() - - moose.reinit() - rdes.displayMoogli( 0.0002, 0.052 ) - -Here we make more extensive use of two concepts which we've already seen -from the single compartment squid model: - -1. *chanProto*: This defines numerous channels, each of which is of the - form: - - ``[ filename ]`` - - or - - ``[ filename, channelname ]`` - - or - - ``[ channelFunction(), channelname ]`` - -If the *channelname* is not specified the system uses the last part of -the channel name, before the filetype suffix. - -2. *chanDistrib*: This defines the spatial distribution of each channel - type. Each line is of a form that should be familiar now: - - ``[channelname, region_in_cell, parameter, expression_string]`` - -- The *channelname* is the name of the prototype from *chanproto*. This - is usually an ion channel, but in the example above you can also see - a calcium concentration pool defined. -- The *region\_in\_cell* is typically defined using wildcards, so that - it generalizes to any cell morphology. For example, the plain - wildcard ``#`` means to consider all cell compartments. The wildcard - ``#dend#`` means to consider all compartments with the string - ``dend`` somewhere in the name. Wildcards can be comma-separated, so - ``#soma#,#dend#`` means consider all compartments with either soma or - dend in their name. The naming in MOOSE is defined by the model file. - Importantly, in **.swc** files MOOSE generates names that respect the - classification of compartments into axon, soma, dendrite, and apical - dendrite compartments respectively. SWC files generate compartment - names such as: - - :: - - soma_<number> - dend_<number> - apical_<number> - axon_<number> - -where the number is automatically assigned by the reader. In order to -select all dendritic compartments, for example, one would use *"#dend#"* -where the *"#"* acts as a wildcard to accept any string. - The -*parameter* is usually Gbar, the channel conductance density in *S/m^2*. -If *Gbar* is zero or less, then the system economizes by not -incorporating this channel mechanism in this part of the cell. -Similarly, for calcium pools, if the *tau* is below zero then the -calcium pool object is simply not inserted into this part of the cell. - -The *expression\_string* defines the value of the parameter, such as -Gbar. This is typically a function of position in the cell. The -expression evaluator knows about several parameters of cell geometry. -All units are in metres: - -- *x*, *y* and *z* coordinates. -- *g*, the geometrical distance from the soma -- *p*, the path length from the soma, measured along the dendrites. -- *dia*, the diameter of the dendrite. -- *L*, The electrotonic length from the soma (no units). - -Along with these geometrical arguments, we make liberal use of the -ternary expressions like *p < 50e-6 ? 500 : 100* or multiplying a channel -density with a logical function or Heaviside function H(x) to set up the -channel distributions. The -expression evaluator also knows about pretty much all common algebraic, -trignometric, and logarithmic functions, should you wish to use these. - -Also note the two Moogli displays. The first is the calcium -concentration. The second is the membrane potential in each compartment. -Easy! - -.. figure:: ../../../../images/rdes8_active.png - :alt: 3-D display for active neuron - - 3-D display for active neuron - -Suggestions: - - - Try another morphology file. - - Try different channel distributions by editing the chanDistrib lines. - - There are numerous predefined channels available within Rdesigneur. - These can be defined using the following chanProto options: - - :: - - ['make_HH_Na()', 'HH_Na'] - ['make_HH_K_DR()', 'HH_K'] - ['make_Na()', 'Na'] - ['make_K_DR()', 'K_DR'] - ['make_K_A()', 'K_A'] - ['make_K_AHP()', 'K_AHP'] - ['make_K_C()', 'K_C'] - ['make_Ca()', 'Ca'] - ['make_Ca_conc()', 'Ca_conc'] - ['make_glu()', 'glu'] - ['make_GABA()', 'GABA'] - - Then the chanDistrib can refer to these channels instead. - - Deliver stimuli on the dendrites rather than the soma. - - -Build a spiny neuron from a morphology file and put active channels in it. -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ - -*ex9.2_spines_in_neuronal_morpho.py* - -This model is one step elaborated from the previous one, in that we now -also have dendritic spines. MOOSE lets one decorate a bare neuronal -morphology file with dendritic spines, specifying various geometric -parameters of their location. As before, we use an swc file for the -morphology, and the same ion channels and distribution. - -:: - - import moose - import pylab - import rdesigneur as rd - rdes = rd.rdesigneur( - chanProto = [ - ['./chans/hd.xml'], - ['./chans/kap.xml'], - ['./chans/kad.xml'], - ['./chans/kdr.xml'], - ['./chans/na3.xml'], - ['./chans/nax.xml'], - ['./chans/CaConc.xml'], - ['./chans/Ca.xml'] - ], - cellProto = [['./cells/h10.CNG.swc', 'elec']], - spineProto = [['makeActiveSpine()', 'spine']], - chanDistrib = [ - ["hd", "#dend#,#apical#", "Gbar", "50e-2*(1+(p*3e4))" ], - ["kdr", "#", "Gbar", "p < 50e-6 ? 500 : 100" ], - ["na3", "#soma#,#dend#,#apical#", "Gbar", "850" ], - ["nax", "#soma#,#axon#", "Gbar", "1250" ], - ["kap", "#axon#,#soma#", "Gbar", "300" ], - ["kap", "#dend#,#apical#", "Gbar", - "300*(H(100-p*1e6)) * (1+(p*1e4))" ], - ["Ca_conc", "#", "tau", "0.0133" ], - ["kad", "#soma#,#dend#,#apical#", "Gbar", "50" ], - ["Ca", "#", "Gbar", "50" ] - ], - spineDistrib = [['spine', '#dend#,#apical#', '20e-6', '1e-6']], - stimList = [['soma', '1', '.', 'inject', '(t>0.02) * 1e-9' ]], - plotList = [['#', '1', '.', 'Vm', 'Membrane potential'], - ['#', '1', 'Ca_conc', 'Ca', 'Ca conc (uM)']], - moogList = [['#', '1', 'Ca_conc', 'Ca', 'Calcium conc (uM)', 0, 120], - ['#', '1', '.', 'Vm', 'Soma potential']] - ) - - rdes.buildModel() - - moose.reinit() - rdes.displayMoogli( 0.0002, 0.023 ) - -Spines are set up in a familiar way: we first define one (or more) -prototype spines, and then distribute these around the cell. Here is the -prototype string: - -:: - - [spine_proto, spinename] - -*spineProto*: This is typically a function. One can define one's own, -but there are several predefined ones in rdesigneur. All these define a -spine with the following parameters: - -- head diameter 0.5 microns -- head length 0.5 microns -- shaft length 1 micron -- shaft diameter of 0.2 microns -- RM = 1.0 ohm-metre square -- RA = 1.0 ohm-meter -- CM = 0.01 Farads per square metre. - -Here are the predefined spine prototypes: - -- *makePassiveSpine()*: This just makes a passive spine with the - default parameters -- *makeExcSpine()*: This makes a spine with NMDA and glu receptors, and - also a calcium pool. The NMDA channel feeds the Ca pool. -- *makeActiveSpine()*: This adds a Ca channel to the exc\_spine. and - also a calcium pool. - -The spine distributions are specified in a familiar way for the first -few arguments, and then there are multiple (optional) spine-specific -parameters: - -*[spinename, region\_in\_cell, spacing, spacing\_distrib, size, -size\_distrib, angle, angle\_distrib ]* - -Only the first two arguments are mandatory. - -- *spinename*: The prototype name -- *region\_in\_cell*: Usual wildcard specification of names of - compartments in which to put the spines. -- *spacing*: Math expression to define spacing between spines. In the - current implementation this evaluates to - ``1/probability_of_spine_per_unit_length``. Defaults to 10 microns. - Thus, there is a 10% probability of a spine insertion in every - micron. This evaluation method has the drawback that it is possible - to space spines rather too close to each other. If spacing is zero or - less, no spines are inserted. -- *spacing\_distrib*: Math expression for distribution of spacing. In - the current implementation, this specifies the interval at which the - system samples from the spacing probability above. Defaults to 1 - micron. -- *size*: Linear scale factor for size of spine. All dimensions are - scaled by this factor. The default spine head here is 0.5 microns in - diameter and length. If the scale factor were to be 2, the volume - would be 8 times as large. Defaults to 1.0. -- *size\_distrib*: Range for size of spine. A random number R is - computed in the range 0 to 1, and the final size used is - ``size + (R - 0.5) * size_distrib``. Defaults to 0.5 -- *angle*: This specifies the initial angle at which the spine sticks - out of the dendrite. If all angles were zero, they would all point - away from the soma. Defaults to 0 radians. -- *angle\_distrib*: Specifies a random number to add to the initial - angle. Defaults to 2 PI radians, so the spines come out in any - direction. - -.. figure:: ../../../../images/rdes9_spiny_active.png - :alt: 3-D display for spiny active neuron - - 3-D display for spiny active neuron - -Suggestions: - - - Try different spine settings. Warning: if you put in too many spines - it will take much longer to load and run! - - Try different spine geometry layouts. - - See if you can deliver the current injection to the spine. Hint: the - name of the spine compartments is 'head#' where # is the index of the - spine. - -