The name of the simulator itself is nbc_x. XNBC V8 is a software to simulate and analyze biological neural networks models. Normally, the control panel displayed by the xnbc command allow to control all the modelling process. Nevertheless, the simulator itself allows to control also, in the same way, all the simulation process, using pulldown menus instead of graphic pushbuttons (Fig. 8.1).
Two models of neurons are available, an enhanced leaky integrator and a Hodgkin-Huxley type model with 14 different ionic currents.
Inputs to the simulated neurons can be provided by data stored in files from actual experiments, allowing to make ``hybrid'' networks. The modelled neurons as well as the network are described using graphic tools.
Neuron and network parameters can be modified during the simulation, to mimick electrical stimulations and drugs action.
After simulation the temporal evolution of the network or those of selected neurons can be visualized, and point process, frequential and dynamic analyzes can be performed.
There exist two graphic editors to adjust the neuron parameters.
XNBC's LIM is derived from the classical leaky integrator implementing properties such as fatigue and post-spike membrane shunt (for a complete description of this model, see Vibert et al., 1994).
The user adjusts the parameters by sliding the scale cursors (right part of the screen), while the temporal evolution of the membrane potential (left part of the screen) changes in real time according to the parameter values. In the LIM, a pacemaker behavior is obtained with a threshold below the resting potential. A small amount of noise can be added to the membrane potential. When the parameters are correctly tuned, the user saves the unit parameters or plot the graph copy.
A conditional burster is also available from the same neuron editor, leading to an BUM (Burster Unit Model).
XNBC's conductance model is derived from the Hodgkin-Huxley (HH) model, and
incorporates 14 different transmembranar currents. This model explicitly
takes into account the Na+, K+, Ca++, and Mg++ ions. The following currents
are implemented by XNBC: INa,
INa + 
, ICa, It,
IK, IM, IA,
IAHP, IC, IH, INMDA, Ileak,
Isynepsp and
Isynipsp. The currents are
modeled using the dynamics of their activation/inactivation constants. All
parameters of the CBM can be individually adjusted. The NMDA receptor for
glutamatergic synapses neuromodulation is also implemented in this model
(for a complete description of this model, see Vibert et al., 1994). The
user adjusts the parameters by moving the double dials cursors (or by typing
the value), while the temporal evolution of the membrane potential and ionic
current (left part of the screen) change in real time according to the
parameter values. The graphic submenu allows to plot any parameter versus
any other parameter in order to study the dynamics of neuron behavior.
Current and voltage clamp experiments can be simulated in order to adjust
the conductance values. Drugs such as TTX and TEA can be released to compare
the neuron behavior with and without the corresponding blocked channels.
In this CBM the pacemaker behavior is obtained by correctly adjusting the Calcium current and the the IA current. The small amount of noise added to the membrane potential irregularizes the interspike intervals. When the parameters are correctly tuned, the user saves the unit parameters.
The postsynaptic potential (PSP) parameters, namely their amplitude, rise and decay time constant, depend on the membrane on which the postsynaptic receptor is, and are consequently a neuron characteristic. The three parameters can be adjusted separately, and are modelled as a modification of the membrane potential or a synaptic current Isyn, according to the chosen model.
The connection matrix of the modeled network can be described using one of the two graphic editors.
The units of one nucleus can be connected with the units of any other nucleus (including itself) through either all excitatory, all inhibitory or both excitatory and inhibitory synapses.
It allows to build nuclei containing only one cluster each. It is made for rapidly build large networks made of several clusters that can be mixed together (CBM, LIM otr virtual). It allows to finely edit the connection matrix.
It does not allow to see individually the neurons inside the clusters, nor to work in Horsley-Clarke coordinates. It does not allow to describe the NMDA connctions.
It allows to build nuclei containing several clusters each. It is made for build small (or large if you have time...) networks made of several clusters that can be mixed together (CBM, LIM otr virtual). It allows to finely edit the connection matrix and to choose the connection density around a given neuron. This is a rather sohpisticated tool.
It allows to see individually the neurons and their connections inside the clusters, and to work in Horsley-Clarke coordinates. Connections with glutamate release acting on NMDA receptors can also be specified.
Each neuron, whatever the model chosen, acts on others via an axon whose length, diameter, transmitter release, etc., are reflected by the delay between the spike in the emitting neuron and the postsynaptic potential (PSP) in the receiving neuron. PSPs can be either excitatory (EPSP) or inhibitory (IPSP). The weight of the connections (the number of synaptic boutons) is distributed using an uniform random distribution. The inter- neural transmission delay can be adjusted. The inter-neural delay in a given nucleus is computed from the user defined mean and standard deviation, and represents the cumulated effect of both the length of the axons and the synaptic delay. Connections are setup graphically by first placing the nuclei in the Horsley-Clarke coordinates, then by populating the nucleus with clusters of neurons and describing the intra nucleus connection pattern. Several convenience tools allow to describe precisely these connections (inter neural connection of neighbor neurons according to a probability curve user shaped, cristal editor for repetitive connection patterns, point to point connection editor). Inter nuclei connections are then described using the same tools.
It is possible to prepare or modify, from the simulator itself, the neuron files or the network files.
This is done using the Menu Modify.
Once the network is built and the iteration step and the duration of the simulation are set, the simulation can be run.
First load a link file (Menu File/New simulation)
Then answer the questions aked by the program (normally answer OK to all the dialog boxes...)
Once the network is loaded, the simulation can begin.
Chose the time step (defaulting to 1ms) (Menu Simulation/Timestep), and the time of the periodic stop that can be programmed (Menu Simulation/Next stop), and the simulation duration (Menu Simulation/Last stop) -this is optional, since you can stop the simulation when you want, interactively-.
Chose the way you survey the simulation process, either by watching at the individual spikes, or at the global activity of the network (partitionned into nuclei) using the Menu Watch/Dot display (individual spikes) or Watch/Global act... (global activity) or again only a counter (Watch/iteration counter or Watch/Millisecnds counter).
The menu Display allows to obtain the conection matrix of weights, or of axon lengths, or agaib the NMDA connection matrix.
During the simulation process, the network behavior can be observed on a graphic display representation.
At any time the simulation can be momentarily stopped by pressed the red STOP button or by typing (CTRL-I) -(CTRL-R or pressing the green RUN button starts again)- in order to modify the external input feeding one or several nuclei, to give stimulation, drug, or change any parameter. It is also possible to modify some anatomical characteristics, such as a connections between two nuclei, mimicking a lesion, or the membrane properties, mimicking pharmacological effects of drugs (Menu Modify and Menu Parameters). The simulation can be stopped at any time, and the network state kept for a further simulation continuation.
Each nucleus can receive external inputs (this is defined during the simulation, not at the level of the network edititor).
It is possible to modify the input or several parameters during the simulation.
This is done using the Menu Parameters.
Then select the nucleus or cluster that must be affected. A dialog box opens, The same dialog box allows to modify all parameters, they grouped into several panels arranged in a ring. Thus selct Next to get the following set of parameters. The OK pushbutton closes the dialog box and validates the modified parameters.
Background gaussian noise, with adjustable mean activity and variability representing the activity of neurons external to the simulated network of neural clusters can be added for each nucleus. Neurobiological experiments, such as electrical stimulations, can also be simulated. XNBC allows to include virtual clusters, treated exactly as the other clusters regarding the connections with the "true" (i.e. simulated) clusters, but where neurons are not modeled. The file may come from a previous simulation or actual experimental data.
At any time the simulation can be momentarily stopped by stroking CTRL-I (Tab) ot the red STOP button or by typing (CTRL-I) -(CTRL-R or pressing the green RUN button starts again)- in order to modify the external input feeding one or several nuclei, to give stimulation, drug, or change any parameter. It is also possible to modify some anatomical characteristics, such as a connections between two nuclei, mimicking a lesion, or the membrane properties, mimicking pharmacological effects of drugs.
The simulation can be started again from the same state by sroking CTRL-R or pressing the green RUN button. The simulation can be stopped at any time [CTRL-I or (Tab)], and the network state kept for a further simulation continuation.
Before to be able to access the simulated data, it is necessary to close the simulation (Menu File/Close (and save files)). This enables the Menu Analysis.
When the simulation is closed, data files can be eitheir visualized or analyzed. Analysis can be made at the level of the individual spike trains using time series dataa anysis tools, or at the level of the global activity of a nucleus.
After the simulation, the color visualization tool can display the behavior of the modeled network along time, using several representations with an adjustable speed and scale. This visualization tool can be seen as a video tape player allowing to run, stop, go to a given iteration, or change the playing speed. Several representations can be displayed (Fig. 8.2:
One is for time series analysis, and is mainly devoted to analyze the individual unit discharges (point process analysis: rate time, interspike intervals, pre and post-stimulus histograms, Poincaré maps of intervals, auto and cross correlograms, etc.). It offers 31 different analysis grouped into 8 submenus. For example it can show interspike interval evolution along time for the noisy sine input and the corresponding cycle triggered histogram (CTH) , a post event histogram triggered by a cycle start.
The other analysis tool is devoted to the analysis of the clusters activity and allows 8 different analysis with FFT, Poincaré maps, auto and cross amplitude correlograms, etc.
It allows to browse the manual.
Input: *.lnk, *.def, *.len, *.wgt, *.clu, *.anat, *.tms, *.neur
Output: *.tms, *.mod, *.sim, *.def, *.pmb, *.prm, *.sim, *.neur
Starting from a saved simulation to continue, existing from version 3, is not yet re-implemented in version 8.
