Auditory cortex layer IV network model (Beeman 2013)

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"... The primary objective of this modeling study was to determine the effects of axonal conduction velocity (often neglected, but significant), as well as synaptic time constants, on the ability of such a network to create and propagate cortical waves. ... The model is also being used to study the interaction between single and two-tone input and normal background activity, and the effects of synaptic depression from thalamic inputs. The simulation scripts have the additional purpose of serving as tutorial examples for the construction of cortical networks with GENESIS. The present model has fostered the development of the G-3 Python network analysis and visualization tools used in this study... It is my hope that this short tutorial and the example simulation scripts can provide a head start for a graduate student or postdoc who is beginning a cortical modeling project. "
Reference:
1 . Beeman D (2013) A modeling study of cortical waves in primary auditory cortex BMC Neuroscience 14(Supl 1):P23
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Auditory cortex;
Cell Type(s): Neocortex V1 pyramidal corticothalamic L6 cell; Neocortex V1 interneuron basket PV cell;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: GENESIS;
Model Concept(s): Activity Patterns; Tutorial/Teaching;
Implementer(s): Beeman, Dave;
Search NeuronDB for information about:  Neocortex V1 pyramidal corticothalamic L6 cell; Neocortex V1 interneuron basket PV cell;
  
Documentation for the ACnet2 GENESIS model
==========================================

I encourage you to extend and share this tutorial/documentation and
simulation script package with others. The files here may be freely
distributed under the terms of the `GNU Lesser General Public License
version 2.1 <figures/copying.txt>`_.

David Beeman
University of Colorado, Boulder
dbeeman@colorado.edu
Tue Sep  3 12:03:30 MDT 2013

Introduction
------------

Cortical waves have been observed in many cortical areas, including the
primary auditory cortex (AI).  For example, see Kral et al. (2009).  The
*ACnet2* model was developed both as a study of the propagation of cortical
waves, and as a tutorial example for the construction of cortical networks.
The simulation scripts are designed to be run with GENESIS 2.3 and are
extensively commented, are easily customizable and are designed for
extension to more detailed models, or conversion to other simulation
systems.  The model is slowly being implemented in GENESIS 3 (G-3)
(Cornelis et al, 2012) and a conversion to neuroConstruct
(http://www.neuroconstruct.org/) is planned.  The scripts will be of
particular interest to those GENESIS network modelers who have not taken
advantage of the ten-fold speed increase available with the use of 'hsolve'
for network simulations.

This package also contains both GENESIS and simulator-independent Python
tools for the visualization and analysis of network activity.

More information about GENESIS can be obtained from http:genesis-sim.org
and Beeman and Bower (1998).

The scientific purpose and simulation results are described in the
published abstract (Beeman, 2013) and in the CNS 2013 poster presentation,
which may be viewed here in two panels:

`Beeman-CNS2013-poster-top.pdf <figures/Beeman-CNS2013-poster-top.pdf>`_

`Beeman-CNS2013-poster-bottom.pdf <figures/Beeman-CNS2013-poster-bottom.pdf>`_

These are to be read left column first, top to bottom, then right column
from top to bottom.

This document describes the model and how to use the provided simulation
scripts to obtain the results shown in Beeman (2013) Fig. 1 (also at the
top right of the poster).  It also suggests experiments that may be tried
with the many configurable options in the scripts, and ways to extend the
model. It is my hope that this short tutorial and the example simulation
scripts can provide a head start for a graduate student or postdoc who
is beginning a cortical modeling project.

The ACnet2 model
----------------

Biologically detailed and realistic models can hope to reproduce the
relevant mechanisms that cause the system's behavior.  But, they have a
very large space of poorly-defined or poorly-quantified parameters to be
explored.  This makes the analysis and interpretation of results very
difficult.  However, simplified models, such as networks of point
integrate-and-fire neurons without dendritic structure, may leave out
important details that affect network behavior.

The ACnet2 model attempts a compromise by restricting the model to a piece
of the thalamorecipient layer (IV) of primary auditory cortex (AI).  It has
has only two populations of neurons, excitatory 'Ex_cells' and inhibitory
'Inh_cells'.  The default configuration of the model is for the Ex_cell
population to be a 48 x 48 grid of 9-compartment pyramidal cells, and for
the Inh_cells to be a 24 x 24 grid of two-compartment basket cells.  The
size of the two grids, cell spacing, and types of cells, as well as the
location of synaptic connections may configured in the main script. Inputs
from other cortical layers were crudely represented by Poisson-distributed
random inputs to provide background levels of firing for the two
populations in agreement with typical measured values.

The model omits the following important features:

* A detailed model of connections from other layers

* Other types of inhibitory channels (e.g.GABA_B, NMDA) and cells (e.g.
  chandelier) with their particular patterns of connections

* gap junctions betweeen inhibitory cells

* Synaptic plasticity (e.g. facilitation, depression, STDP)

This simplification nevertheless leaves the weighted synaptic conductances
for the four types of connections as poorly known adjustable parameters.
The scaling and balancing of these conductances depends strongly on the
assumptions made on cell density and the connection probablity between
cells as a function of separation.  The goal of this modeling effort was to
find a suitable set of the four maximal synaptic conductances (gmax).  This
should allow the propagation of waves of excitation with neither widespread
undamped oscillations nor excessive inhibitory quenching of the response
to stimuli.

The top right portion of the CNS poster describes how the default
parameters (shown in the `Runtime GUI <figures/0001C_run.png>`_) produce
propagation and constructive interference from two tone inputs to the
model.  Although the input model provides for a realistic spread of
thalamic inputs that have typically observed spike time distributions at a
given characteristic frequency, this example used single row excitations
from spike trains of 220 and 440 Hz, in the absence of background input.

The cell models
---------------

The main features of the two cell models are shown in the figure below.

.. image:: figures/AC_cells.png

The morphology and passive parameters of the pyramidal cell are based on
the reduced neocortical pyramidal cell models of Bush and Sejnowski (1993).
The passive symmetric compartmental model was transformed to an equivalent
asymmetric model by a method that scales compartment dimensions to preserve
the passive properties of each compartment.  The resulting cell has the
same input resistance of 47 Mohm and membrane time constant of 10 msec.
The soma contains voltage and calcium activated channels, and there are
dual-exponential synaptically activated channels at appropriate locations
on the dendrites.  The basket cell is a simple 'ball and stick' model with
a 40 micrometer diameter soma and a 200 x 2 micrometer cylindrical
dendrite.  It has an input resistance of 113 Mohm and a time constant of 10
msec.

The active channels used in the soma are a small set of modified Traub
et al. (1991) hippocampal CA3 region channels with activation and
inactivation time constants scaled to give dynamics typical of neocortical
cells.	Parameter searches were performed manually and with the GENESIS 2
parameter search library simulated annealing method (Vanier and Bower,
1999) to approximately fit current clamp results by Nowak et al. (2003)
for regular spiking cells in cat visual cortex, and by Hefti and Smith
(2000) for rat layer V primary auditory cortex.

The connection model
--------------------

Some neocortical models assume all-to-all connections with a constant small
probability, such as 0.02.  Others use a larger fixed connection
probability over a specified region, but have a synaptic weight factor that
decays with separation distance.  Recent studies of excitatory and
inhibitory synaptic connectivity show that the connection strength is
relatively independent of distance, but that the probability falls off with
a Gaussian probability with distance.  Thus, in accordance with
experimental measurements on cat AI by Yuan et al.  (2008) and rescaled
results for mouse AI by Levy and Reyes (2011, 2012), a fixed connection
weight (taken as 1.0) was used, and the probability for both excitatory and
inhibitory connections was taken to vary with radial distance r in the
layer as::

  P(r) = P0 * exp(-(r/s)^2), with the s = 10*SEP_X = 0.4 mm

  P0(Ex->Ex) = 0.15, P0(Ex->Inh) = 0.45, P0(Inh->Ex) = P0(Inh->Inh) = 0.6

For this model, the separation between excitatory cells SEP_X = 40 micrometers.
The maximum range for connections was 1 mm. This connection scheme
may be easily modified in the main simulation script to corresond
to measurements from other cortical areas.

Many simple cortical models ignore axonal conduction delays.  Experiments
with this model showed that in order to produce propagation of waves of
excitation, the conduction delays should be large enough to produce a
sufficient delay in the onset of inhibition after excitation.  This could
not be achieved by merely increasing the time constant for the inhibitory
conductance.  Estimates for the conduction velocity of short (< a few mm)
intralaminar unmeyelinated axons are in the range of 60-90 mm/s. (Salin and
Price, 1996).  Values for longer distance axons between other cortical
layers or regions are generally higher, ranging from 0.2 to 0.3 m/sec.
(Shlosberg et al. 2008).  This simulation uses the default axonal
conduction velocity of 0.08 m/sec, or a delay of 12.5 sec/m. This delay can
have a significant effect in the delay of the onset of inhibition, as
connected cells 400 um apart can have a delay of 5 msec.

In addition to the interconnections between the cells, the excitatory cells
receive a Poisson-distributed random activation at their basal dendrites in
order to represent excitatory inputs from other layers.  The default
parameters and average frequency (8 Hz.) were chosen in order to give
background levels of firing for the two populations in agreement with those
measured by Steriade et al. (2001).

The runtime GUI
---------------

The screen capture of a typical simulation run 
shows the Control Panel with the simulation
parameters.

.. image:: figures/0001C_run.png 

These parameters were used to produce the network activity shown in
the 'netview' replay of the results.

.. image:: figures/C0003Aasc_prop-sm.png

The sequence of frames at times from 0.8060 (frame A) to 0.8138 (frame E)
represent the soma membrane potential of each excitatory cell on the 48 x
48 grid at the left.  These are an indication of firing or changes in the
subthreshold potential.  Those on the right give their post-synaptic
currents due to excitatory connections (EPSCs) from other pyramidal cells.
These show initial responses to the two tone input produce a growing wave
of excitation past the initial responses of the input rows, culminating in
constructive interference in the middle shown in frame E. 

The plots shown in the runtime GUI are for the middle cell in the labeled
row.  Thus, the 'Ex_cell Membrane Potential' plot shows that there are
pulses of firing in the middle cells of rows 12 and 36, corresponding
to the left netview displays.  The 'Ex_cell synaptic currents' plots
can be related to the right column EPSC display.  These plots are useful
in tuning the synaptic conductances to achieve a good balance of
excitation and inhibition.

The input model
---------------

The input model provided by the default simulation is specialized to
represent the tonotopic organization of inputs from the ventral division of
the medial geniculate body (MGBv). This is the primary source of thalamic
inputs to the primary auditory cortex.	The description of the scripts
further below tells how the input model may be modified to represent other
types of inputs, for example when using the network to model other cortical
areas.

The default parameters give a 48 x 48 network of Ex_cells with rows
numbered from 0 to 47, and a 24 x 24 network of Inh_cells with rows
numbered from 0 to 23. (These are determined from the parameters Ex_NY and
Inh_NY.) However, inputs are not provided to cells in the bottom 8 and top
8 rows, in order to avoid edge effects.  As a result, there is an array of
Ex_NY - 16 = 32 input "thalamic cells", which are numbered from 1 to 32.
Each one of these sources of spike trains targets a row of Ex_cells with a
row number that is offset by 7 from the input number.  This accounts for
the entries in the 'input_control' form below the Control Panel, where
Input 29 is to Target row 36.  Initially, the inputs are assigned a
frequency on a logarithic scale from 220 Hz to 538.584 Hz with a default
set of pulse parameters, and are disconnected.  By specifying an input
number corresponding to the row to be activated, these parameters may be
changed, and the Spike Train toggle set to 'ON', as shown above.

Providing the identical input to an entire row of cells produces more
correlation in the inputs than one would expect from thalamic connections.
One alternative would be to have a two-dimensional array of thalamic
inputs.	 The approach taken in this simulation is to have an 'input_delay'
for each connection from an input to the row of cells, and an
'input_jitter' factor that provides a random 'jitter' in the arrival time
of the input to each cell in the row.  This is implemented with a random
delay uniformly distributed between input_delay*(1 - input_jitter) and
input_delay*(1 + input_jitter).	 The default values of these are 0,
but a reasonable amount of decorrelation can be provided with
input_delay = 0.002 seconds, and input_jitter = 0.4.  These can be set
separately for each input via the 'input_control' GUI.

Once set, the delays with jitter are the same at each time step.  They
represent a decorrelation between the inputs to a row, not a true jitter in
spike arrival time.  Yet, thalamic inputs are known to have a jitter in the
time at which they arrive at their targets. A typical value would be
0.0005, or 0.5 msec.  As described below in the 'Overview of the simulation
scripts', this may be changed from the default of zero with the variable
'spike_jitter'.

There are yet more options for providing more realistic thalamic inputs.
In addition to providing other options for the type and distribution of the
inputs, there is a parameter 'input_spread'.  This the number of rows below
and above the "target row" getting thalamic input.  Typical values span
about one-third of an octave.  The implementation in simple_inputs.g
function *connect_inputs* creates connections with an exponentially
decaying probablility to adjacent rows +/- input_spread.
The default value used here is 0 (thalamic connections are only to the
target row), but a line in the main script can be changed to set it
to 1/6 of an octave, or any other value.

Running the simulation
----------------------

Of course, the first step in running the simulation is to have GENESIS 2.3
installed.  If you have not used GENESIS before, it is simplest to download
the entire 'Ultimate GENESIS Tutorial Distribution' package with all source
code, installation instructions, and the complete set of tutorials
(about 50 MB) from `http://genesis-sim.org/GENESIS/UGTD.html
<http://genesis-sim.org/GENESIS/UGTD.html>`_.  GENESIS usually installs without
problems under modern versions of Linux.  Most questions related to
installation have been answered in the archives of the 'genesis-sim-users'
mailing list, which are available from the GENESIS 2 Sourceforge page at
`http://sourceforge.net/projects/genesis-sim/
<http://sourceforge.net/projects/genesis-sim/>`_.

*ACnet2-main.g* is the main simulation script, with default values of
the parameters that were used to generate the results in Beeman (2013).
It includes the files to create the GUI and contains many configurable
options.

*ACnet2-batch.g* is a stripped down version with fewer options and no
graphics.  Once GENESIS 2.3 has been installed, the command::

  genesis ACnet2-batch.g

runs the simulation with the parameters used to generate the figure in
Beeman (2013). It creates the output files that can be displayed with
the Python G-3 Network View tool in this package, printing messages
such as::

  Starting connection set up:  Sun Aug 11 14:47:17 2013
  (many dots and debugging messages)
  Finished connection set up:  Sun Aug 11 14:49:39 2013

  All maxium synaptic weights set to 1

  Using simple pulsed spiketrain input
  ....
  time = 0.000000 ; step = 0
  time = 0.000000 ; step = 0          
  time = 0.000000 ; step = 0
  Network of 48 by 48 excitatory cells with separations 4e-05 by 4e-05
  and 24 by 24 inhibitory cells with separations 8e-05 by 8e-05
  Random number generator seed initialized to:  1369497795

  Average number of Ex_ex synapses per cell:  36
  Average number of Ex_inh synapses per cell:  36
  Average number of Inh_ex synapses per cell:  109
  Average number of Inh_inh synapses per cell:  35
  time = 0.000000 ; step = 0          
  time = 0.000000 ; step = 0          
  dt = 1.999999949e-05   tmax = 1
  RUNID:  B0003
  START:	Sun Aug 11 14:49:41 2013
  END  :	Sun Aug 11 14:53:01 2013

  genesis #0 >

At this point, you can type 'quit' to the prompt.

Note the significant amount of time spent setting up the connections.  It
is nearly as long as the time to run the model for 1 second. This is
because a GENESIS script language (SLI) function *planarconnect_probdecay*
was used to loop over source and destination cells.  Some suggestions for
implementing this as a compiled GENESIS command are given in the section
'Experiments to try'.

The 'RUNID' is a string that is given a default value in the simulation
script, and can be changed in the GUI for *ACnet2-main.g*. When
*ACnet2-batch.g* is run, it is used to produce output files with names:

* run_summary_B0003.txt - a summary of simulation parameters, read by replay_netview10.g

* Ex_netview_B0003.txt - a file containing the membrane potential Vm for
  each Ex_cell at time intervals 'netview_dt', which is 0.2 msec, the
  slowest 'clock' used in this simulation.

* Inh_netview_B0003.txt - Vm for the Inh_cells

* EPSC_netview_B0003.txt - for each Ex_cell, contains the net Excitatory
  Post Synaptic Current (EPSC) due to connections from other Ex_cells.
  The format is similar to the  Ex_netview file.

* EPSC_sum_B0003.txt - the EPSC summed over all Ex_cells in the network at
  each time step 'out_dt' ( = 0.0001 sec).  This has been related to
  signals detected by MEG and the Power Spectral Density (PSD)
  (Vierling-Claassen et al, 2008), which can be calculated with the
  analysis tools provided here.

The netview files are plain text with a header line in a format that is
described in comments in the main script.

The section below 'Python data analysis and visualization tools' tells how
to generate the `wave propagation results <figures/C0003Aasc_prop-sm.png>`_.

Running ACnet2-main.g
---------------------

Running the simulation from the GUI is similar, with the command::

  genesis ACnet2-main.g

After the connections have been set up, with similar messages to the
console, a GUI similar to the `Runtime GUI <figures/0001C_run.png>`_
will appear.  The default RUNID of "0000" can be changed to another string
of your choice (no spaces or other unix-unfriendly characters).  The output
files will contain this string in place of 'B0003'.  At this point, the
network will get a random Poisson activation at 8 Hz, and no thalamic
input.  To get wave propagation results, set the Random Background
Activation Freq to 0, and use the 'input_control' GUI to provide
the inputs::

  Input 5 (Target Row 12) Input freq 220
	  'Toggle to Spike Train ON'

  Input 29 (Target Row 36) Input freq 440
	  'Toggle to Spike Train ON'

leaving the pulse parameters as given.  This will produce 50 msec tone
'pips' 150 msec apart.

**Don't forget the GENESIS/XODUS eccentricity that you have to hit 'Enter'
or click the mouse in a text field (xdialog) after you edit it, in order
for the changes to register.**

Then click RESET and RUN.  After the run has completed, you may use
interactive GENESIS commands to inspect the model, or click on QUIT.

On examining the output files, you will notice that the 'netview' files
have the extension '.dat' instead of '.txt', and that the elapsed time
to run is about a minute shorter than with ACnet2-batch.g.  That is
because ACnet2-main.g specifies the option 'binary_file = 1', producing
output in the GENESIS 'FMT1' binary format.  This is faster than
with text files, and the files are much smaller.  It also allows
some spike analysis which is not yet possible with the Python tools.
However, when the *bzip2* compression utility is used, the text files
are much smaller than the binary files.  The section 'GENESIS data analysis
and visualization tools' describes some of the analysis and visualization
that can be done using the binary files.

Python data analysis and visualization tools
---------------------------------------------

The directory *Gpython-tools* contains several Python scripts that were
developed for use with the analysis and visualization of results from
simulations carried out with both GENESIS 2.3 and G-3.  They use plain text
data files with optional header information, and some can read text files
that have been compressed with the *bzip2* utility, making data storage
very efficient.  New tools and documentation will be added to this
directory in future updates of the ACnet2 distribution, and will become
available through the `GENESIS Documentation Homepage
<http://genesis-sim.org/userdocs/documentation-homepage/documentation-homepage.html>`_.
The documentation for the present version of *Gpython-tools* is in the file
`Gpython-tools/README.html <Gpython-tools/README.html>`_.

These make use of the *maplotlib* and *wxpython* libraries, which must be
installed. When *netview-I.py* is installed in your search path, it can be
used to provide the animation from which the frames in the `wave propagation
figure <figures/C0003Aasc_prop-sm.png>`_ were taken.

To reproduce the results from running the ACnet2-batch.g, bring up two
instances of *netview-I.py* for the Vm and EPSC data files::

  $ netview-I.py Ex_netview_B0003.txt &
  $ netview-I.py EPSC_netview_B0003.txt &

You will have to click and drag the second netview window off of the first.
The Help menu 'Usage and Help' selection provides a pop-up window telling
you how to use the program, as with many of the tools in this collection.

In each window, click 'New Data'. When the message 'Data has been loaded' appears
you can click 'Play', to replay the entire run.  The frames shown in the
poster are at times::

    A: 0.8060
    B: 0.8072
    C: 0.8082
    D: 0.8112
    E: 0.8138

To reproduce them, drag the 't_min' bar to 0.79 and the 't_max' bar to
0.80, then click 'Play'.  Then repeatedly click 'Single Step' until the
time display is 0.806.  Continue for each of the next times, and compare to
the results in the `wave propagation figure
<figures/C0003Aasc_prop-sm.png>`_.

There are also tools to calculate the PSD of the summed EPSC file.
*plotPSD.py* averages the PSD from a wildcard list of times series data
files, such as the 'EPSC_sum_B0003.txt' file. *plotPSD0.py* is similar, but
it overplots the spectra on the same graph. A typical usage would be::

    $ plotPSD.py EPSC_sum_M0005*
    Plottting average of  4 runs from series  M0005
    EPSC_sum_M0005B.txt EPSC_sum_M0005D.txt EPSC_sum_M0005E.txt EPSC_sum_M0005.txt

For a single file with a run time of only 1 second such as
EPSC_sum_B0003.txt (produced by running ACnet2-batch.g), they both yield the
same low resolution plot.  The PSD plots shown in the lower right column of
the poster were generated from averages of four ten second runs that used
different random number seeds.

GENESIS data analysis and visualization tools
---------------------------------------------

The GENESIS script *replay_netview10.g* and its included files
*analysis_funcs5.g* and *spectra_funcs3.g* are scripts that perform
visualization and spike train analyis on the binary 'netview' files that
are generated with the option 'binary_file = 1'.  These use a fairly
confusing mixture of XODUS graphical objects, spike generators, and obscure
uses of the GENESIS *table* object in order to generate a number of useful
analyses and plots that are not yet available with the Python tools.

In order to set up the graphics and analysis tools, *replay_netview10.g*
needs to read the default 'run_summary_0000.txt' and other files that are
generated from a run of *ACnet2-main.g* with the default RUNID = "0000".
Once these has been done you can type::

    genesis replay_netview10.g

and use "0000" or another RUNID that has existing data.

Windows will appear for for Vm plots, Ex_netview, Inh_netview and
EPSC_netview, as well as

*summary_form* - Displays the run summary file in a scrolling text window

*histform* - A Firing rate distribution histogram for the Ex_cells in the
network.  This will typically by Gaussian, although a model with STDP
should show a lognormal distribution.

*freq_form* - Displays the Average Spike Frequency for Ex_cells and
Inh_celsl with time, with a settable time bin size.  This is particularly
useful when balancing conductances to give proper background firing rates
and fluctations in the rate.

*spectra_form* - Hidden under the freq_form, it calculates the PSD using
a slow Discrete Fourier Transform implemented in the GENESIS scripting
language.  On a modern PC, the performance is not too bad, taking a little
over 20 seconds.  However, the Python 'plotPSD' tools are better suited for
spectral analysis.

Then, click 'RUN' (or first enter the RUNID for another run for which you have files).

You will find that the spike frequency calculations will have produced a
new output file 'spike_freq_0000.txt' that did not exist before.  The
*rowrateplot.py* utility in the `Gpython-tools
<Gpython-tools/README.html>`_ directory can be used with the
'spike_freq_<RUNID>.txt' files to create displays, similar to the `average
spike frequency display <figures/freqplot_C0003A-new.png>`_ shown at the
left of the top poster panel.  This display of the time course of the
average firing rate on a row can be useful in detecting propagation of
neuron firing from row to row.  Note that replay_netview10.g outputs
data for only the 32 'target rows' that receive inputs, so that the
display will normally not show all 48 rows.  (This is a feature of
replay_netview10.g, not of rowrateplot.py.)

Experiments to try
------------------

Here are some suggestions of both simple and challenging things that can
be done to explore or extend the model.

**Changes in parameters through the GUI**

Most important model parameters can be changed through the GUI of
ACnet2-main.g.  The 'gmax' values for the four types of synaptic
connections (which can also be scaled by the 'Weight' value) are a good
place to start.

The default values of the four synaptic conductance values shown in the
`Run Time GUI <figures/0001C_run.png>`_ are more arbitrary than other
parameters. The assumption that the variable Inh_inh_gmax = 0.0, made also
in the model of Levy and Reyes (2011), produced a balance of excitation and
inhibition that resulted in an appropriate average background firing rate
for the inhibitory cells (about 22 Hz.) The GABA conductance of basket
cells, and their mutual connection probability are poorly known. However it
seems reasonable that there be some degree of mutual inhibition between
basket cells.

The poster mentions an alternate set of gmax values that increased the
basket cell AMPA conductances to 0.3 nS and provided mutual inhibition with
a 0.1 nS basket cell GABA conductance, These resulted in similar background
firing rates, but less robust wave propagation. However, this resulted in
a better match of the EPSC spectra to experiment.  Clearly, there is a lot
of parameter space to explore with this small set of parameters.

Wave propagation is strongly affected by the axonal conductance delay
(the inverse of conduction velocity).  How much less than 12.5 sec/m
can the network have and still support wave propagation?

The frequency and strength (gmax) of the random background activation can
be varied.  The results shown in the poster used zero background
activation, because it was difficult to observe the response to
the input in the presence of strong backgrond activity.  Studies
of propagation in the presence of background should be done.

Parameters for the thalamic input can be varied either by setting
the Ex_cell and Inh_cell gmax for thalamic input, or by setting
parameters for individual inputs.  What is the effect of increasing
or decreasing the strength of the thalamic input?

There is much yet to be explored regarding the interaction of nearby
cells that receive auditory inputs.  Do these parameters allow lateral
inhibition of closely spaced tones?

As described on the section 'The input model', the 'Input delay' and 'Input
jitter' values can produce a more realistic variation in the input received
by the cells within a row.

**Changes by editing the option strings in the main script**

There are many global parameters that are used for the initial setup
of the network, and that cannot be changed from the GUI.  The section
'Overview of the simulation scripts' below describes the option strings
and global variables that can be changed.

Of course, any serious use of the network for auditory modeling should
extend the length of the network along the y-axis (the tonotopic axis)
to cover a wider range of octaves. 

The time constants tau1 and tau2 for the synaptic conductances have a major
effect on the balance of excitation and inhibition, the default values are
based on reasonable estimates from available data, but there is some
uncertainty in the time constants for the rise and decay of inhibition.
(Because of a bug in hsolve, these cannot be changed from the GUI after
the network has been set up.)

How much of the results are due to the particular set of probabalistically
assigned connections? The random number seed is set to a fixed value in the
main script.  This allows you to reproduce these results, but you will
certainly want to change it in order to compare multiple runs with
different connections.

**Providing more realistic auditory inputs**

The section on 'The input model' describes the 'spike_jitter' parameter, in
addition to the GUI-settable 'Input delay' and 'Input jitter' values.  This
parameter can be set in order to see if fluctuations in spike arrival time
affect the network behavior in a significant way.

The restriction that the thalamic inputs do not extend beyond cells on the
'target row' was made in order to simplify the analysis of wave
propagation.  It would be more reasonable to extend the range with
the parameter 'input_spread'.  This will probably require modifications
in the thalamic drive weight and some rebalancing of the gmax for
the four types of connections between cells.

The assumption that the output of thalamic cells is a uniform spike train
at the frequency of the sound source is probably a good one for low
frequency 'click trains', but not for tones of 220 or 440 Hz.  In order to
provide a more realistic distribution of input spike train intervals, one
might develop a more detailed thalamic (MGBv) cell model for inputs to the
network.  Some early work by Roullier et al. (1979) on unanethesized cats
provides histograms of spike time distributions.  A simpler alternative is
to experiment with the alternate option string input_type =
"pulsed_randomspike".  Can you see any significant differences?

The options for 'input_pattern' give an opportunity to explore other
non-auditory inputs.  Customizing these will involve changes to some
parameters in the script 'simple_inputs.g'.  For example, the "box" input
pattern can be used to study a spiking neurion model analgous to the model
of Rule et al. (2011) to simulate flicker phospenes in visual cortex.

The poster also describes experiments that can be performed on the model
to study the power spectra of responses to 20 - 40 Hz click trains.

**Speeding up the connection setup**

The definition of *function planarconnect_probdecay* shows how the
algorithm is impelmented.  It is similar to what is used in the C code for
planarconnect2, defined in the GENESIS source file
*genesis/src/newconn/connect.c*.  The GENESIS Reference Manual in the
'UGTD' or the help files in *genesis/Doc* give detailed instructions on
implementing new commands and objectsi in GENESIS.  This could be a fairly
simple project for someone with some experience in hacking other people's C
code.

**Adding synaptic plasticity** (suitable for an advanced project)

The most serious feature lacking in the model is any form of synaptic
plasticity. Spike Timing Dependent Plasticity (STDP) and other forms of
plasticity are important effects in auditory and other cortical areas.  It
would be a productive next step in the evolution of the ACnet2 model to
incorporate a phenomenological STDP model such as the one by Song, Miller
and Abbott (2000).  It is perhaps better to understand the effect of these
mechanisms on this simple two population network before extending the
network model to include connections to other layers or other types of
neurons.

Implementing STDP will require some hacking of the GENESIS 2.3 source code
and/or modifications (and bug fixes) to the contributed stdpSynchan library
from the 'Libraries' collection at `http://genesis-sim.org
<http://genesis-sim.org>`_.  Also see the GENESIS documentation for
'Creating New Synaptic Objects'.  Simpler methods of adding plasticity
would be to use the GENESIS 'hebbsynchan' or 'facsynchan' objects.  These
have the restriction that they cannot be used with the 'hsolve' object, and
cannot take advantage of its efficient delivery of spike events.

The simulation scripts
----------------------

*ACnet2-main.g*, the main simulation script, directly or indirectly includes:

*pyr_4_asym.p* - The cell parameter file that describes the excitatory
pyramidal cells in the network.

*pyr_4_sym.p* - This file is not used in the scripts, but is offered for
those who may want to implement the pyramidal cell model with symmetric
compartments instead of asymmetric compartments.

*bask.p* - The cell parameter file that describes the inhibitory basket
cells in the network.

*protodefs.g* - Defines a library of components (compartments, channels,
etc.) that are used to create the cells

*pyrchans.g* - Defines the functions that create the pyramidal cell channels.

*FSchans.g* - Defines the functions that create the basket cell channels.

*synapseinfo.g* - Inclusion of this file is optional.  Comments in the file
tell how to use the function *synapse_info(path)* to get information
about the connections in a network.

*graphics2-5.g* - Defines functions to create the main GUI of
control panel and graphs.

*input_graphics2-5.g* - Provides an additional GUI for setting the
array of inputs to the model.

*simple_inputs.g* - This defines the two functions *make_inputs* and
*connect_inputs* that are used by the main script.  *make_inputs* creates an
array of "cells" that mimic the output of auditory thalamic cells (MGBv).
*connect_inputs* connects the array of of inputs to the network cells.

The simplified *ACnet2-batch.g* script does not include the graphics files,
and includes a simplified *basic_inputs.g* script instead of
*simple_inputs.g*.


Overview of the simulation scripts
----------------------------------

Here are some notes to help you make changes to the default simulation
scripts, either by simple edits to the option strings and global variables,
or by modifications to the commands and functions that are described
below. If you would like to make significant changes, and are new to
GENESIS SLI script hacking, it would be useful to look through the `GENESIS
Modeling Tutorial
<http://genesis-sim.org/GENESIS/UGTD/Tutorials/genprog/genprog.html>`_
from the GENESIS web site.  The section 'Creating large networks with
GENESIS' provides a tutorial on the construction of a simpler model
'RSnet', and explains the use of the GENESIS commands for creating networks
and setting synaptic weights and delays.  For the complete set of tutorials
with source code for GENESIS 2.3 and PGENESIS, download the entire package
(about 50 MB) from `http://genesis-sim.org/GENESIS/UGTD.html
<http://genesis-sim.org/GENESIS/UGTD.html>`_

The main script ACnet2-main.g is profusely commented, and contains
citations for the sources of most parameter values.  The script
(and ACnet2-batch.g, with fewer options) begins with the definitions
of the simulation and output time steps and default run time (1 sec),
and a 'RUNID" string that will be used in the names of the
several simulation output files that are generated.

then it defines some flags to control which options are used.  The
more useful ones define the output of the simulation::

  int batch = 0 // if (batch) run the default simulation without graphics
  int graphics = 1     // display control panel, graphs, optionally net view
  int netview = 0      // show network activity view (slow, but pretty)
  int netview_output = 1	// Record network output (soma Vm) to a file
  int binary_file = 1	// if 0, use asc_file to produce ascii output
 			// else use disk_out to produce binary FMT1 file
  int write_asc_header = 1 // write header information to ascii file
  int EPSC_output = 1  // output Ex_ex EPS currents to file
  int calc_EPSCsum = 1 // calculate summed excitatory post-synaptic currents

With these defaults, the GUI implemented in graphics2-5.g and
input_graphics2-5.g will be used to control the simulation and
display results.  The network activity view will not be displayed,
but the data to generate the display will be output in binary format.
These will be the soma Vm of all the cells and the net Excitatory Post
Synaptic Current (EPSC) that each pyramidal cell "apical3/AMPA_pyr"
channel receives from other pyramidal cells.

These determine the type of connection to be used::

  int use_weight_decay = 0 // Use exponential decay of weights with distance
  int use_prob_decay = 1 // Use connection probablility exp(-r*r/(sigma*sigma))
  int connect_network = 1  // Set to 0 for testing with unconnected cells

Some network models use a constant connection probability over some
region (use_prob_decay = 0), and then compensate by weighting more
distant connections with a lesser weight factor.  This model
use the more realistic assumptions that the effectiveness
of synaptic connections does not appreciably decrease with
distance, but connection probability follows a roughly Gaussian
decay with distance.

You will likely not want to change these::

  int hflag = 1    // use hsolve if hflag = 1
  int hsolve_chanmode = 4  // chanmode to use if hflag != 0
  int use_sprng = 1 // Use SPRNG random number generator, rather than default

Without hsolve, the simulation will run approximately ten times slower.
However, you will not be able to use hsolve if your cell model contains any
custom objects or others that are not hsolveable.  The default GENESIS 2
random number generator does not give an unbiased distribution, and it is
better to use the SPRNG random number generator.

The next definitions describe the inputs to the model::

  str input_type = "pulsed_spiketrain"  // pulsed spike train input
  // str input_type = "pulsed_randomspike"   // pulsed input from a randomspike
  // str input_type = "MGBv" // input from simulated thalamic cells

  str input_pattern = "row"     // input goes to an entire row of cells
  // str input_pattern = "line" // input to specified line of cells within row
  // str input_pattern = "box"  // input to a square block of cells

The sequence of spikes generated depends on the string 'input_type', which
can be either "pulsed_spiketrain" or "pulsed_randomspike".  The pattern of
connections from a member of the "input cell" array to the network cells is
determined by string 'input_pattern'.  These options and the ones further
below for input_delay, input_jitter, spike_jitter, and input_spread have
been described above in the section 'The input model'.

The line::

  int seed = 1369497795

guarantees that the same set of connections and inputs will be used each
time the simulation is run, and to produce the results shown in Beeman
(2013).  Change it to 0 for new random numbers each time, or to another
seed value to explore other configurations.

This is followed by some strings that specify the cell parameter files and
names for the Ex_cells and Inh_cells, and paths to the synaptic
conductances for the various locations for synaptic input.  It is a simple
matter to plug a different set of cell models into this network by changing
these.  Next come the definitions for the size and spacing of the two grids
of cells::

  int Ex_NX = 48; int Ex_NY = 48
  int Inh_NX = 24; int Inh_NY = 24

  float Ex_SEP_X = 40e-6
  float Ex_SEP_Y = 40e-6 
  float Inh_SEP_X = 2*Ex_SEP_X  // There are 1/4 as many inihibitory neurons
  float Inh_SEP_Y = 2*Ex_SEP_Y

and default values of the synaptic conductances and their time constants.

After definitions of many functions for setting paramwter values (called
either from the GUI, or later in the script) come the important functions
for setting up the network.  The definition of::

  function planarconnect_probdecay(src_cell_path, src_spikepath, n_src, \
      dst_cell_path, dst_synpath, n_dst, rmin, rmax, prob0, sigma)

is worth studying, as it can be modified to change the distribution and
probabilities of connections beteen cells.  (It is also a candidate for
more efficient implementation in C.)  It is indirectly called by function
*connect_cells*, which sets these arguments to *planarconnect_probdecay*.

This is followed by other functions to set weights and delays.
The functions for file output of results are worth studying to understand
the format of the files, and to see how 'findsolvefield' is used with
'hsolve' to access data values.

The 'Main simulation section' creates, the cell prototypes, creates the
unconnected network of Ex_cells and Inh_cells, and sets a number of
paramters.  The statements following 'if(hflag)' are a guide to using
hsolve with a network simulation.  Note the network is created first, a
solver is created for only on cell of each type, and then duplicated for
the other cells.  There is more information on tricks with hsolve in the
hsolve documentation and in the advanced tutorial `Simulations with GENESIS
using hsolve <http//:genesis-sim.org/GENESIS/UGTD/Tutorials/advanced-tutorials>`_.

After 'simple_inputs.g' is included, the functions *make_inputs* and
*connect_inputs* are called.  Study this file if you would like to explore
alternate input models.  Note that hsolve allows you to create connections
and change weights and delays *after* hsolve has been set up.

After some more parameter setting and optional inclusion of the graphics
GUIs and outputs, the program ends with::

  if(batch)
      // set up the inputs for the default simulation with two inputs:
      // Row 12 -  220Hz, Row 36 - 440 Hz
      set_frequency 0.0 // No background excitation
      setfield /MGBv[5]/spikepulse level1 1.0 
      setfield /MGBv[5]/spikepulse/spike abs_refract {1.0/220.0}
      setfield /MGBv[29]/spikepulse level1 1.0
      setfield /MGBv[29]/spikepulse/spike  abs_refract {1.0/440.0}
      reset
      reset
      step_tmax
  end

To run the simulation in batch mode, set the options strings::

  int batch = 1 
  int graphics = 0

You may set the 'binary_file' flag as you like, and edit the 'setfield'
commands above to produce the desired input.


References
----------

Beeman D (2013) A modeling study of cortical waves in primary auditory
cortex. BMC Neuroscience, 14(Suppl 1):P23 doi:10.1186/1471-2202-14-S1-P23
(`http://www.biomedcentral.com/1471-2202/14/S1/P23
<http://www.biomedcentral.com/1471-2202/14/S1/P23>`_.)

Bower JM, Beeman D (1998, 2003) The Book of GENESIS: Exploring Realistic
Neural Models with the General NEural SImulation System, second edn.
Springer-Verlag, New York. Free internet edition available at:
http://genesis-sim.org/GENESIS/iBoG/iBoGpdf

Bush PC, Sejnowski TJ (1993) Reduced compartmental models of neocortical
pyramidal cells, J Neurosci Methods 46:159-166

Cornelis H, Coop AD, Bower JM (2012) A Federated Design for a
Neurobiological Simulation Engine: The CBI Federated Software Architecture.
PLoS ONE 7(1): e28956. doi:10.1371/journal.pone.0028956

Hefti BJ, Smith PH (2000) Anatomy, physiology, and synaptic responses of
rat layer V auditory cortical cells and effects of intracellular GABAA
blockade.  J Neurophysiol 83:2626-2638.

Kral A, Tillein J, Hubka P, Schiemann D, Heid S, Hartmann R, Engel AK
(2009) Spatiotemporal Patterns of Cortical Activity with Bilateral Cochlear
Implants in Congenital Deafness. J Neurosci 29::811-827.

Levy RB, Reyes AD (2011) Coexistence of Lateral and Co-Tuned
Inhibitory Configurations in Cortical Networks. PLoS Comput Biol 7(10):
e1002161. doi:10.1371/journal.pcbi.1002161

Levy RB, Reyes AD (2012) Spatial profile of excitatory and inhibitory
synaptic connectivity in mouse primary auditory cortex, J Neurosci
32:5609-5619.

Nowak, LG, Azouz R, Sanchez-Vives MV, Gray CM, McCormick DA (2003)
Electrophysiological classes of cat primary visual cortical neurons in vivo
as revealed by quantitative analyses. J Neurophysiol 89:  1541-1566.

Roullier EM, de Ribaupierre Y, de Ribaupierre F (1979) Phase locked
responses to low frequency tones in the medial geniculate body.
Hearing Research 1:213-226.

Rule M, Stoffregen M, Ermentrout B (2011) A Model for the Origin and
Properties of Flicker-Induced Geometric Phosphenes.  PLoS Comput Biol.
7(9): e1002158. doi: 10.1371/journal.pcbi.1002158

Salin PA, Prince DA (1996) Electrophysiological mapping of GABAA
receptor-mediated inhibition in adult rat somatosensory cortex.
J Neurophysiol 75:1589-600.

Shlosberg D, Abu-Ghanem Y, Amitai Y (2008) Comparative properties of
excitatory and inhibitory inter-laminar neocortical axons. Neuroscience
155:366-373.

Song S, Miller KD, Abbott LF (2000) Competitive Hebbian learning
through spike-timing-dependent synaptic plasticity. Nat Neurosci 3:
919-926.

Steriade M, Timofeev I, Grenier F (2001) Natural Waking and Sleep States: A
View From Inside Neocortical Neurons J Neurophysiol 85: 1969-1985.

Traub RD, and Robert K. S. Wong RKS, Miles R, Michelson H (1991) A Model of
a CA3 Hippocampal Neuron Incorporating Voltage-Clamp Data on Intrinsic
Conductances J Neurophysiol 66: 635-650.

Vanier MC, Bower JM (1999) A comparative survey of automated
parameter-search methods for compartmental neural models. J Comput Neurosci
7: 149-171.

Vierling-Claassen D, Siekmeier P, Stufflebeam S, Kopell N (2008)
Modeling GABA alterations in schizophrenia:
a link between impaired inhibition and altered gamma and beta range
auditory entrainment. J Neurophysiol 9:2656-2671. doi: 10.1152/jn.00870.2007

Yuan K, Shih JY, Schreiner CE, Winer JA (2008) GABAergic network
differences between auditory cortex areas.  Unpublished data from
Soc Neurosci Abstr poster 67.12.


Beeman D (2013) A modeling study of cortical waves in primary auditory cortex BMC Neuroscience 14(Supl 1):P23

References and models cited by this paper

References and models that cite this paper

Cornelis H, Coop AD, Bower JM (2012) A federated design for a neurobiological simulation engine: the CBI federated software architecture. PLoS One 7:e28956 [PubMed]

Rodriguez AL, Cornelis H, Beeman D, Bower JM (2012) Multiscale modeling with GENESIS 3, using the G-shell and Python BMC Neuroscience 13(Supl 1):P176

(2 refs)