------------------------------------------------------------------------------ LEECH HEART INTERNEURON 8-CELL TUTORIAL HELP Andrew Hill, Steve Van Hooser, Ron Calabrese ------------------------------------------------------------------------------ This tutorial allows one to study a network model of the leech heart interneuron by Andrew Hill and Ron Calabrese. Note: This help describes how to run the model, perform experiments, and view the results. For a general introduction to the leech heart interneuron circuit or a technical description of the model, please see the "Introduction". For help using one of the specific experiment tools, use the "Help" button on its window. ------------------------------------------------------------------------------ TABLE OF CONTENTS: (1). Viewing the introductory material (2). Showing, hiding, and viewing graphs (3). Experiments (4). Running the model and setting initial conditions ------------------------------------------------------------------------------ (1). VIEWING THE INTRODUCTORY MATERIAL The "Introduction" is an HTML document which can be viewed in a web browser. Clicking on the introduction button brings up a small window with a text field that says: "netscape <filename>", where <filename> is the name of the introduction document. If you use a different web browser, simply change the name from "netscape" to the name of your browser. If you do not have an web browser at all, please see the Calabrese lab FTP site for a postscript version of the introduction. Use username "anonymous" and get the file pub/tutorials/intro.ps on calabreselx.biology.emory.edu. ------------------------------------------------------------------------------ (2). SHOWING, HIDING, and VIEWING GRAPHS There are six windows containing graphs of the activity of the network which can be alternatively shown and hidden. Two contain membrane voltage traces, and four contain current traces for the various currents in HN cell 4L (this cell was arbitrarily chosen). To show the membrane voltage for all of the left or right cells, click "Show Left Vm's" or "Show Right Vm's". A window will pop up with the appropriate voltage traces, and the button will change its name to "Hide <Left/Right> Vm's". Clicking on "Hide..." will hide the window. To show the ionic current flowing in HN cell 4L, click on either "Show 4L INa, IK" or "Show 4L Ih, ICa, IP". The former shows the fast sodium current and the three potassium currents, and the later shows the current activated by hyperpolarization, the fast and slow calcium currents, and the persistent sodium current. Clicking on the button again will hide the window, just like the membrane voltage windows above. To show the synaptic current flowing into cell 4L, click on either "Show 4R->4L currents" or "Show 1,2L->4L currents". These show the synaptic currents to cell 4L from cell 4R or from cells 1,2L, respectively. Clicking on the button again will hide the window, just like the above windows. All of the graphs have several features in common. First, all graphs have a "scale" button which can be used to change the minimum and maximum values for the x- and y-axes. Second, there is a button on the top of the set of graphs labeled "Autoscale", which will automatically adjust the time axes to run from time 0 to until the end of the currently-running simulation (as determined by the value in the "Time (sec)" field). Finally, one can adjust the scale of an axis graphically by clicking on the maximal or minimal label, holding down, and dragging to a new value. For example, to change the voltage axis to be from (0..-0.060) to (0..-0.030), simply click on the label "-0.060", drag until hitting the value -0.030 on the axis, and release. The graph will redraw with the new scale. To change it back, simply grab onto the "-0.030" label, and drag off the graph until hitting -0.060 and release. ------------------------------------------------------------------------------ (3). EXPERIMENTS At present, one can perform three manipulations on the model. First, one may change its parameters using the "Parameter Editor"--simply click on the button to use it. The Parameter Editor has its own help feature, so look there for detailed information on using the editor. Second, one may inject current into any of the cells by clicking on the "Current Injection" button and adjusting the value for each cell. Remember that the units are in Amps, and that typical current injections for neurons are in the tenths of a nano-Amp range. To inject 0.1e-9 into the HN cell 4L, simply edit the text field next to "cell_4L" to read 0.1e-9, and then either press return or click on the label "cell_4L". Finally, one may disable cells and synapses. While in principle one may set the synaptic weights of any cell in which one is not interested to zero to remove its contribution, one can save time by not computing the activity of that cell at all. The "Disable Cells and Synapses" tool allows one to "disable" these cells so they are not updated in the simulation. Further, it is common to set the value of a synaptic weight to zero and then return it to its original value. One can do this by entering the specific values in the "Parameter Editor", but a feature to do this more quickly has been added in the "Disable Cells and Synapses" tool. See that tool's help button for more information. Special note: If you disable a cell, be sure to disable the synapses leading away from the cell because otherwise the disabled cell will continue to output the same synaptic current it did the instant it was disabled. ------------------------------------------------------------------------------ (4). RUNNING THE MODEL AND SETTING INITIAL CONDITIONS To run the model, simply specify how long the simulation should last in the "Time" field and then click "Run". Clicking "Stop" during a simulation will stop the simulation. Clicking "Reset" will reset the simulation clock and return the values of the simulation components to the original initial values. (Note that this leaves the parameters of the model untouched, but returns variables such as the current flowing into the cell and the membrane voltage to their original initial values.) Clicking "Exit Tutorial" will quit the program and GENESIS. The "Kick" button and the "Initial Cond" button allow the initial conditions to be adjusted for different model parameters. This is important for two reasons: first, it is possible to start two cells which normally fire out of phase in exactly the same state, and, since this is a computer simulation without noise, the model doesn't start oscillating. Second, even if the cells are started at slightly different values, it may take a long time before the cells settle into their oscillation pattern. The "Kick" command solves both of these problems--it briefly injects negative current into all of the cells to quiet them, and then releases one group of cells which fire together in the animal. It runs, in total, for 0.4 sec, and restores any previous injection value when it is finished. If one is using a set of parameters that take a long time to settle down, one may want to let the system settle down one time and then save the state of the network for later restoration. Pressing "Initial Cond" exposes a hidden set of buttons that allow the user to do just this. Simply type the name of a file to save and either press return or click the label of the text edit box. To restore a set of conditions that were saved, enter the name in the "Restore" text box and either press return or click the text box label. To restore the default initial condition, simply click the button with that label. Clicking "Initial Cond" again will hide the buttons from the user. ------------------------------------------------------------------------------