THE IMPACT OF INPUT FLUCTUATIONS ON THE FREQUENCY-CURRENT RELATIONSHIPS IN A BIOPHYSICAL NEURON MODEL (1)Arsiero, M., (1)Luescher, H.-R., (2)Lundstrom, B.N., and (1,3)Giugliano, M. (1) Institute of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland (2) Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA. (3) Laboratory of Neural Microcircuitry, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne - EPFL, CH-1015 Lausanne, Switzerland Corresponding author: Michele Giugliano, mgiugliano@gmail.com, http://www.giugliano.info This package is running with the NEURON simulation program written by Michael Hines and available on internet at: http://www.neuro.duke.edu/neuron/home.html It contains mechanisms (.mod files) and programs (.hoc files) needed to simulate the biophysical model, modified from the standard Hodgkin-Huxley model, as described in the following submitted manuscript Arsiero, M., Luescher, H.-R., Lundstrom, B.N., and Giugliano, M. (2007) The Impact of Input Fluctuations on the Frequency-Current Relationships of Layer 5 Pyramidal Neurons in the Rat Medial Prefrontal Cortex. sumbitted. The paper examines in vitro frequency vs. current (f-I) relationships of layer 5 (L5) pyramidal cells of the rat medial prefrontal cortex (mPFC) using fluctuating stimuli. Studies in the somatosensory cortex show that L5 neurons become insensitive to input fluctuations as input mean increases and that their f-I response becomes linear. In contrast, mPFC L5 pyramidal neurons retain an increased sensitivity to input fluctuations, while their sensitivity to the input mean diminishes to near zero. A phenomenological approach, based on a novel Integrate-and-Fire model is presented and employed to describe quantitatively the data and to quantify the statistical significance of the new finding. An underlying biophysical mechanism for the observed phenomenon is proposed, based on a slow inactivating component of the sodium current. The NEURON package provided here aims at giving the readers the possibility of reproducing the simulations of the paper (Figure 4A), in the case of a standard Hodgkin-Huxley model (1952), modified to include a slow inactivation component as described by Miles et al. (2005). The NEURON package thus include two new mechanisms: 1) a fluctuating current-clamp injection, to mimick the experiments; 2) a modified Hodgkin-Huxley model, including the additional gate variable. The gate variable and its kinetics are from the contribution of Miles et al., (2005). This model can be used to produce an ASCII text file (i.e. TF.x), containing the mean firing rate for each combination of input current mean and variance. A simple matlab script is then provided to plot such results. By opening the main simulation file 'runme.hoc' and modifying line 14 (i.e. the value of a_hhin) is possible to include or exclude the additional slow inactivation of sodium channels Questions on how to use this model should be addressed to Michele Giugliano (mgiugliano@gmail.com) Under unix systems: =================== to compile the mod files use the command nrnivmodl and run the simulation hoc file with the command nrngui runme.hoc Under Windows: ============== to compile the mod files use the "mknrndll DOS box" and follow on-screen instructions. A double click on the simulation file runme.hoc will open the simulation window.