Add model cell types and specify model cell numbers and connections

This tutorial will illustrate the necessary steps to add another interneuron type to the ca1 model network, such as perforant path-associated cells (PPA cells). First, we would need to create a new model cell template for this cell type, and then we would need to create some datasets containing information about how to incorporate that cell type into the model network. We will walk through both of these goals in the following tutorial.

The tutorial will begin by copying an existing, working model cell template. It is a good idea to create the model cell template by adapting it from an existing file. Users can make incremental changes to a copy of the working template to ensure that they maintain the standardization and functionality of the template and also to ensure the ability to check that the template still works after each change.

  1. First make a copy of the Schaffer Collateral-Associated (S.C.-A) cell template, as the S.C.-A. cell type is quite similar to the PPA cell type. Within the ’cells’ subdirectory of the model repository, open the ’class_scacell.hoc’ file and choose ’Save As’ and then type ’class_ppacell.hoc’. Now the new cell template is ready to be edited and tuned to become a model PPA cell.
  2. Next, rename the template within the file. The first and last code lines of the file refer to the template name, which should be ’ppacell’ instead of ’scacell’. To work most efficiently, use find and replace to change all references to ’scacell’ to ’ppacell’ in the document.
  3. Next, alter the morphology and electrophysiological properties defined in the file as we see fit. Later on, there will be an opportunity to test and further tune the cell using the CellClamp tool to ensure that it behaves as a physiological PPA cell.
  4. Finally, save the file and then return to the SimTracker tool to add the cell to the network model. Now that the model PPA cell template has been created and added to the ’cells’ directory, it is time to create the new datasets that will include this cell type in the network.
  5. From the SimTracker ’Tools’ menu, choose the ’Cell Numbers’ option.
  6. A dialog box will open, allowing the user to select an existing cell numbers set or to create a new set that specifies which cell types to include in the model and how many of each should be included. To create a new set based on the existing set #101, choose 101 from the top menu to load that cell numbers dataset.
  7. Before making any changes, click the ’Save New...’ button and add a comment to the box that appears, stating ’#101 with ppacell added.’ This will save a new dataset that can be edited.
  8. Now, from the celltype menu, select ’ppacell’ on both sides and then click ’Add’.
  9. A new line will be added with an entry for ’ppacell’, Enter the remaining information on that line, including the number of ppacells in the full size network and the layer in which they are found (stratum lacunosum-moleculare is layer 3, since stratum oriens is layer 0).
  10. Next, click the ’Save’ button. A dialog box will appear stating that a new axonal distribution file has been created for the ppacell. To specify the axonal extent and distribution of boutons of the ppacell, modify its axondist file from within the axondists directory of the cells directory in the repository. Further information about this file and its parameters is included in the User Manual.
  11. Now, close the Cell Numbers dialog box.
  12. Next, from the SimTracker ’Tools’ menu, choose ’Connections’. A matrix will appear. From the top left menu, select ’430’ to load the basic dataset from which we will derive our new one. Then, from the top right menu, select the number corresponding to the new cell numbers dataset just saved. The matrix will now expand to include ppacells as well. Down the left side of the matrix (the row labels) are given the presynaptic cells, while the top row (the column labels) gives the postsynaptic cells. At the intersection of each presynaptic and postsynaptic cell, add the average number of connections from all cells of that presynaptic type onto one postsynaptic cell of that type (aka, the convergence).
  13. After filling out all the connection information for connections to or from ppacells (convergence numbers, synapses per connection, and synaptic weights), save the connection tool and close it.
  14. Finally, from the ’Tools’ menu choose ’Synapses.’ A table will appear. From the top left menu, select the number ’120’ to load a baseline synapse dataset.
  15. Then, from the top right menu, select the number corresponding to the recently created cell numbers dataset that contains the PPA cells.
  16. Now, notice the pop-up menu at the top middle to specify a post-synaptic cell. Select the ppacell from this menu and then add potential presynaptic cells to the list to specify their specific kinetics. Save the dataset by clicking the ’Save’ button.
  17. Now, switch the top middle menu to each cell that can receive input from the PPA cell in turn. Add the synaptic entry for the ppacell connection. Then, before switching to a different post-synaptic cell, again save the current table. After completing the definitions for all postsynaptic celltypes, then save the table again and push the button to close. One of each type of the parameter dataset has been created to specifying the network and its connections: cell numbers, connections, and synapse kinetics. These datasets resemble those used in the control CA1 network simulation except that they also include PPA cells. Now, users can launch the CellClamp tool, set the dataset menus in it to the ones just created, and test both the intrinsic cell properties of the PPA cell and the connections to and from PPA cells (using the paired recording feature). The next tutorial covers the use of the CellClamp tool.

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