All the model files are in model_files directory. This directory has 4 subdirectories: long_dend, which contains model files for spatial simulations of a 20 um long dendrite; model_70_percent, model_100_percent and model_120_percent contain files for simulations of a short dendrite. model_100_percent is the basal model, model_70_percent and model_120_percent were used for robustness evaluation. All the scripts used in analysis and to generate the figures are in directory scripts. To successfully run a model, you need the master model file, which specifies reaction file, initial conditions file, morphology file, stimulation file and output config file. Run the simulation using version 2.1.10 of NeuroRD. This version of the java program is called stochdiff2.1.10.jar and is located in scripts/. To run NeuroRD: java -jar stochdiff2.1.10.jar <model_file> NeuroRD generates two files: one ending with '-mesh.txt', which specifies morphology, the other ending with '-conc.txt' containing amounts of molecular species (specified in output config file) in the region specified in output config file. Names of master model files start with "Model_one_short_dendrite_PKAc_times_3_switching_L_pump_neurogranin_" for the short dendrite simulations and "Model_long_dendrite_PKAc_times_3_switching_L_pump_neurogranin_" for the long dendrite simulations. Initial conditions file names start with "IC_switching_steady_L_pump_neurogranin", reaction file names start with "Reac_gradedkdiff_PKAc_times_3_gigs_switching_L_pump_neurogranin", stimulation files start with "Stim_" and morphology files start with "morph". If the master file (or any other file) was used for simulations of bath application of bAR agonists and antagonists, or blocked PKA conditions, it is also indicated in the file name. Probably the safest thing is to have all the model files (of a particular model) in one directory. An alternative method of running the simulations is to use the python script: generate_initial_specie_information.py usage: python get_initial_specie_information.py <model_master_file> <length of the simulation> [other options] get_initial_specie_information.py will make a new master_file with the ending runtime_[length of the simulation].xml If you run get_initial_specie_information.py without specifing the runtime, the script will run the simulations for one simulation step and generate a new master model file <master model file>_runtime_<simulation step>.xml and a new output file <master model file>_whole_output.xml. The output config specifies providing output for every molecule in the simulation. It will generate a new output config file (using initial conditions file) unless one specifies not to (e.g. for the long dendrite simulations). This python script is very convenient for simulating the short dendrite, however, for simulations of the longer denrite, you might want to use a custom output config file (only getting output of a subset of the molecules) to make the simulations a bit faster and concentration files smaller. --help gives all the options of get_initial_specie_information.py (also how to specify custom output file). Additional information on generate_initial_specie_information.py: If you use this python script to run your simulations, you will have to change the neurord path inside the code or specify it in command line using --path. If you use it without --no_run switch, the model will either run for a specified time (in ms) or for dt and add runtime_{specified time} to the models filename. I run my models with --segment_concentrations and --segment_list=PSD,head,neck to get concentrations in the spine and dendrite. You can get_initial_specie_information.py also to generate concentrations while model is still running. One can use the same python script to perform just the analysis with a --no_run switch. --chosen_species will prevent generating the output config file and instead use the custom one specified in the master model file. I use make_figures.py to look at concentrations of individual molecular species. To generate Tables S1 and S2 use check_thresholds.py and check_thresholds_dendrite.py respectively. Both scripts also contain information about the path of data files used to generate tables. Please update them to match your directory tree. Running multispine models I also use get_initial_specie_information.py. Here I specify a custom output file (Long_dend_output.xml) because the data files are huge and difficult to analyze. I use --segment_concentrations and then use make_full_spines.py to obtain specie concentrations in the spines. For species used in dendritic signature I use extract.py. I generated figures using averaged traces (obtained with make_average.py). I use multispine_statistics.py to get duration above the threshold for individual traces. To generate figure 10 use new_way_spines.py (with averaged traces). config.py and config_long.py are the main files governing figures, specifying which file names to use to plot data. You will have to update those paths to match your directory tree. function.py contains all the functions I used. Fig 3 was generated using Epac_comparison.py Fig 4 was generated using 2_panel_signatures.py Fig 5 was generated using 4_panel_figure.py Figs 6&7 were generated using synaptic_tags_camkii_calibration_standard_paradigms_only_epac.py Figs 8&9 were generated using propranolol_carvedilol.py Fig 10 was generated using glurs_2_panel.py Fig 11 was generated using new_way_spines.py To extract data from conc files I used extract.py and make_full_spines.py Fig 11 was generated using fig_12.py, model files are in fig_12 directory