=========== Model files for simulating the cofilin signaling pathway underlying hippocampal LTP

Signaling pathways include:

1. Calcium influx through the NMDA receptor leading to activation of AC1 and AC8, calcineurin, CaMKII  

2. Norepinephrine, Beta-androgenic receptor, couple to G protein leading to an increase of cAMP, thus PKA activation  

3. Cofilin activation via Ca/CaMKII and cAMP/PKA: Rac, PAK, SSH and LIMK 

.. figure:: https://github.com/neurord/cofilin/blob/master/Cofilin_diagram.jpg :alt: ERK signaling pathwway diagram :figclass: align-center

**Figure: Schematic representation of signaling pathways activating Cofilin**

Note: 1 and 2 are (from published model (Jȩdrzejewska-Szmek, J., Luczak, V., Abel, T., Blackwell, K.T., 2017. β-adrenergic signaling broadly contributes to LTP induction. PLOS Computational Biology 13, e1005657.)

Model_Cofxxx.xml contains the entire model specification, which combines Reaction file (Rxn_Cof.xml*), Morphology file (Morph.xml*), initial conditions file (IC_Cof.xml*), output file (Out_Cof.xml*) and stimulation (Stim_Cof.xml*). To run simulations, use NeuroRDv3.3.0:

``java -jar /path/to/neurord-3.2.4-all-deps.jar /path/to/Modelfile.xml``

All output files were first processed using nrdh5_analv2 in https://github.com/neurord/NeuroRDanal

Main folder: Reaction files, stimulation files and Morphology files and updated IC files used in all simulation.

Subfolders:

Init:

1. To match the in vitro data on basal concentration, simulate the model for about an hour to obtain steady-state concentrations for all molecules 

2. To copy basal quantities of molecules, run: ARGS="h5_filename -sstart ssend -IC IC_filename -Rxn Rxn_filename -tot tot_species_filename" (-tot is optional) 

then exec(open('path/to/file/UpdateIC_basal_spatial.py').read()) 

Exp_1spine: Model files for simulation with 2 um long dendrite with 1 spine

Exp_5um_3spines: Model files for spatial simulation with 5 um long dendrite with 3 spines

Exp_10um_3spines: Model files for spatial simulation with 10 um long dendrite with 3 spines

The Model reaction kinetics and molecule quantities are summarized in Cofilin_parameters.xls.