Network Clamp a cell using the NetworkClamp tool

Next, use the Network Clamp tool to employ the Network Clamp technique [BRB+16] on the model. The Network Clamp is most useful for a large network, especially one with many inputs to each cell. The Network Clamp tool can be used for investigating how various inputs affect individual cells and for studying network dynamics without requiring a supercomputer. For this example, we will study how a particular cell’s behavior changes as a function of the strength of the incoming synapse. This will gives us an idea of how to alter our connectivity strength in the full model without having to run a lot of full-network simulations to find the proper synapse strength. We will run this tutorial from the ca1 repository, so please ensure that SimTracker currently has the ca1 repository open before proceeding. The first few steps of the tutorial describe how to download the results and configuration [BezaireSciData] from the control, full scale CA1 network run used in [BRB+16], so that they can be used as the basis for a network clamp run in the rest of the tutorial.

  1. First, download the CA1 control simulation results from Open Science Framework: https://osf.io/v4ceh/
  2. Then, from within SimTracker, choose File > Import and select the newly downloaded ca1_centerlfp_long_exc_065_01 file to import it. The simulation run should then appear in the SimTracker runs table.
  3. From the SimTracker Tools menu, choose “Network Clamp” and the Network Clamp tool will open.
  4. Within the Network Clamp tool, at the top left area in part “1. Inputs”, select the “Simulation Results” radio button.
  5. Then, from the popup menu next to it, choose the network simulation to use as the baseline: “ca1_centerlfp_long_exc_065_01” and change the duration from 4000 to 100 (ms).
  6. Next, find the popup menu for “Use inputs for” and choose “pyramidalcell (21310 - 332809)”, and for gid number, enter 21310.
  7. For part “2. Electrophysiology”, choose the electrophysiology of “poolosyncell”, which is the technical cell template used in the model CA1 network, derived from the pyramidal cell model published by [Poolos02].
  8. Finally, for part “3. Connections”, choose to use the connections and synapses from the corresponding network simulation by clicking the “From Run” radio button for the Connections line as well as for the Synapse kinetics line. Then verify that the “Run” menu below says “ca1_centerlfp_long_exc_065_01”, as the simulation run from which to take the connections and synapse kinetics.
  9. At the bottom left area, enter a description for this Network Clamp run, such as “Running baseline netclamp for pyramidal cell”, click the “Table View” radio button for “Results” and then click the “Execute” button.
  10. After the run completes, the intracellular membrane potential recording for the cell will appear on the graph on the right side, as well as histograms of each input type received by the cell throughout the simulation. In the table at the top right, a summary of the run will appear. Users can toggle whether the design or the results of the network clamp run are shown using the radio buttons at the bottom left of the NetClamp tool. Next, try altering the inputs to this cell and observing the effect. This tutorial will arbitrarily focus on investigating the effect of distal feedback inhibition, which is mediated by neurogliaform cell inputs on the pyramidal cell.
  11. In part “3. Connections” on the left side of the NetworkClamp, switch the connections radio button to “Custom Table”. Then in the table below, find the row for input cell “ngfcell” (for neurogliaform cell) and the column for “Wgt (uS)”. Change the value from 1.4500e-04 to 1.4500e-05, decreasing by 90% the incoming weight of inhibition from neurogliaform cells to the network-clamped pyramidal cell.
  12. In the description field at the bottom left of the tool, enter a new description of “90% reduction of neurogliaform cell input” and then click “Execute” button. The simulation will run again with all the same times of spike inputs to the pyramidal cell, and the incoming synaptic weights and kinetics will remain the same for all inputs except for neurogliaform cell inputs. The neurogliaform cell inputs will occur at the same time, with the same kinetics, but have a synaptic amplitude that is only 10% of the baseline condition.
  13. After a few minutes, a new record will appear in the upper right table and a new trace will appear on top of the old one in the graph just below it. The input histograms will update to reflect the inputs from this new run.
  14. Various run results can be hidden or displayed by clicking the checkbox next to the corresponding description in the results table. The color and dash pattern of each results line can also be customized by adjusting the settings in columns “Col” and “Line” of the results table. Currently, the input histograms always display the input spike times from the most recent network clamp simulation run.
  15. Now, try running a Network Clamp simulation that uses patterned stimulation input designed by the user, rather than stimulation based on the activity of a large scale network simulation result.