This is the readme for the models associated with the paper Peter Jedlicka, Thomas Deller, Boris S. Gutkin, Kurt H. Backus (2011) Activity-dependent intracellular chloride accumulation and diffusion controls GABAA receptor-mediated synaptic transmission Hippocampus 21:885-898. Send bug reports, comments and questions on how to use this model to jedlicka@em.uni-frankfurt.de/mohapatra@em.uni-frankfurt.de The code for 8 granule cell morphologies and passive properties was taken from Schmidt-Hieber et al. 2007: http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=95960 See their readme file for the description of .hoc files in the ./share and ./cell_x folders. Usage: 1. Download and install NEURON (available from http://www.neuron.yale.edu/neuron/download) 2. Compile the NEURON mod files: mswin: run mknrndll and select this folder to create the nrnmech.dll linux: run nrnivmodl in this folder mac os x: drag and drop this folder onto mknrndll 3. Start the simulations: Figure 6 simulation - EGABA shift following activation of multiple GABAA synapses: ------------------------------------------------------------- mswin: double click the mosinit.hoc file using windows explorer linux: type "nrngui mosinit.hoc" in the shell prompt in this folder mac os x: drag and drop the mosinit.hoc file onto the nrngui icon To run the simulation click on Init & Run button. The simulation automatically executes stochastic activation of multiple dendritic and somatic GABA-A synapses with mean frequency of 10 Hz/synapse. The simulation starts running and begins to generate a shape plot of the granule cell, with colour code indicating EGABA changes. The simulation reproduces Figure 6A of the paper, but since the synapses are activated randomly, each run's result is unique. Zooming in on one of the simulation generated figures should look like: - Note: Default cell morphology is cell_7. This can be changed in the ./share/controlpanelGC.hoc file by changing defaultCellIndex variable (ranging from 0 to 7). Figure 7 simulation - EGABA shift following activation of a single GABAA synapse: --------------------------------------------------------------------- mswin: double click the mosinit_single.hoc file using windows explorer linux: type "nrngui mosinit_single.hoc" in the shell prompt in this folder mac os x: drag and drop the mosinit_single.hoc file onto the nrngui icon To run the simulation click on Init & Run button. The simulation automatically executes stochastic activation of a single dendritic GABA-A input with mean frequency of 40 Hz. The simulation starts running and begins to generate a shape plot of the granule cell, with colour code indicating EGABA changes. - Note: Default location of the synapse is in the middle of a dendrite. This can be changed in the ./init_ClmIPSCs_GC_single.hoc file by setting DISTAL_SIMULATION = 1 (to move the synapse to the distal end of the dendrite). For further simulation parameters please refer to the paper. Description of mod files: ./cldifus.mod Chloride radial/longitudinal diffusion and accumulation mechanism with chloride extrusion mechanism mediating exponential recovery of intracellular chloride concentration to resting chloride level. ./cldifus2.mod Chloride radial/longitudinal diffusion and accumulation mechanism with chloride pump (Lineweaver-Burke equation) and chloride leak. Not used in Fig6/7 simulations. ./gabaA_Cl.mod Ohmic synaptic GABAergic mechanism with dynamic GABA reversal. ./gaghk.mod GHK synaptic GABAergic mechanism with dynamic GABA reversal. Not used in Fig6/7 simulations.