Readme for model associated with the paper Prescott SA, De Koninck Y. (2005) Integration time in a subset of spinal lamina I neurons is lengthened by sodium and calcium currents acting synergistically to prolong subthreshold depolarization. J Neurosci. 25(19):4743-54. Abstract: Lamina I of the spinal dorsal horn plays an important role in processing and relaying nociceptive information to the brain. It comprises physiologically distinct cell types that process information in fundamentally different ways: tonic neurons fire repetitively during stimulation and display prolonged EPSPs, suggesting operation as integrators, whereas single-spike neurons act like coincidence detectors. Using whole-cell recordings from a rat spinal slice preparation,weset out to determine the basis for prolonged EPSPs in tonic cells and the implications for signal processing. Kinetics of synaptic currents could not explain differences in EPSP kinetics. Instead, tonic neurons were found to express a persistent sodium current, INa,P , that amplified and prolonged depolarization in response to brief stimulation. Tonic neurons also expressed a persistent calcium current, ICa,P , that contributed to prolongation but not to amplification. Simulations using NEURON software demonstrated that INa,P was necessary and sufficient to explain amplification, whereas INa,P and ICa,P acted synergistically to prolong depolarization: initial activation of the slower current (ICa,P) depended on the faster current (INa,P) but maintained activation of the faster current likewise depended on the slower current. Additional investigation revealed that INa,P and ICa,P could dramatically increase integration time (>30X) and thereby encourage temporal summation but at the expense of spike time precision. Thus, by prolonging subthreshold depolarization, intrinsic inward currents allow tonic neurons in spinal lamina I to specialize as integrators that are optimally suited to encode stimulus intensity. Model Notes: Model demonstrates mechanism whereby two kinetically distinct inward currents act synergistically to prolong subthreshold depolarization. The important currents are a persistent Na current (with fast kinetics) and a persistent Ca current (with slower kinetics). Model also includes a slow K current and transient Ca current, in addition to standard HH currents. Model parameters are set to values used in Fig. 8A. Simulation shows prolonged depolarizations in response to two brief stimuli. Usage: Auto-launch from ModelDB (unix and pc). Press init and run() button. Alternatively download the zip archive. Then depending on your platform: mswin: Expand the archive. Run mknrndll and traverse to the newly created directory and click make the nrnmech.dll Then double click the mosinit.hoc file in windows explorer. Unix: Expand the archive with unzip *.zip Compile the NEURON mod files by running nrnivmodl in the newly created directory. Type nrngui mosinit.hoc to start the simulation mac OS X. Drag and drop the zip file on the mos2nrn icon in the Neuron application folder. The mod files are automatically compiled and the simulation starts automatically. --- Note: The voltage-gated mechanisms have been revised to allow adaptive integration, rather than fixed time step integration with dt = 0.01 ms as was done in the paper. This allows the simulation to run faster without loss of accuracy. Also, the initial membrane potential has been changed from -63 to -62.65 mV, which is the resting potential for this particular model implementation.