<html><pre> Author: Oscar Javier Avella Gonzalez (oscarjavella at gmail.com) This model was implemented in the Simulation Environment NEURON version 7.1 and uses Matlab V.209bb-2014b to analyze the data. All routines are based on general functions of this platform. Main paper: Oscar Javier Avella Gonzalez, Huibert D. Mansvelder, Jaap van Pelt, Arjen van Ooyen (2015). H-channels affect frequency, power and amplitude fluctuations of neuronal network oscillations. Front. Comput. Neurosci.9. doi:10.3389/fncom.2015.00141 <a href="http://www.frontiersin.org/Journal/Abstract.aspx?s=237&name=computational_neuroscience&ART_DOI=10.3389/fncom.2015.00141">http://www.frontiersin.org/Journal/Abstract.aspx?s=237&name=computational_neuroscience&ART_DOI=10.3389/fncom.2015.00141</a> The model and the whole set of routines are released under the GNU GPL version 3: <a href="http://www.gnu.org/copyleft/gpl.html">http://www.gnu.org/copyleft/gpl.html</a> Purpose of this work: This model was designed to study the impact of H-currents on the dynamics of cortical oscillations, and in paticular on the occurrence of high and low amplitude episodes (HAE, LAE) in network oscillations. The H-current is a slow, hyperpolarization-activated, depolarizing current that contributes to neuronal resonance and membrane potential. We characterized amplitude fluctuations in network oscillations by measuring the average durations of HAEs and LAEs, and explored how these were modulated by trains of external spikes, both in the presence and absence of H-channels. We looked at HAE duration, the frequency and power of network oscillations, and the effect of H-channels on the temporal voltage profile in single cells. We found that H-currents increased the oscillation frequency and, in combination with external spikes, representing input from areas outside the network, strongly decreased the synchrony of firing. As a consequence, the oscillation power and the duration of episodes during which the network exhibited high-amplitude oscillations were greatly reduced in the presence of H-channels. Impaired expression of H-channels, with both up- and downregulation occurring, is associated with the pathology of epileptic disorders (Chen et al., 2001; Biel et al., 2009). Our results are consistent with the observed effects of altered H-channel expression in epilepsy. For example, as in the model, upregulation of H-channels in hippocampal CA1 neurons leads to an increased probability of action potential firing and a higher firing frequency (Chen et al., 2001). Model Description: The model consisted of a network of 80 excitatory (E) cells and 20 inhibitory (I) cells, interconnected with AMPA (excitatory) and GABAA (inhibitory) synapses. The synaptic strengths and connection probabilities were chosen so as to produce a strong PING-like (pyramidal-interneuron gamma) rhythm. The conductance-based cells had a single compartment with K+ Na+, leak and H-channels. Running the simulation: The model was originally ran in NEURON 7.1 using the conventional command-line scheme, edited in pspad (but any other text editor also works). Either autolaunch from ModelDB or download the archive and compile the mod files in the mods/network_sims_MODs folder. See <a href="http://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.html">http://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.html</a> for more help. To set up the simulation example, go to /main directory and load the file "RunSimulation.hoc" Once the windows are open, press the button "single run" in the MultipleRuncontrol panel. The simulation will start, running for 40000ms. When the simulation stops, expand the window "Pyram Cells Population # 0" in the horizontal axis, to check the dynamics of the excitatory population (rastergram). <img src="./fig1.png" alt="fig 1" width="550"> Do the same for the window labeled Fast Spiking Cells Population #0 and check the inhibitory population dynamics. <img src="./fig2.png" alt="fig 2" width="550"> The results of this "program run" are automatically saved in the file './output_h_test/WW_example_ONLY_ih.m' Producing the example figure: The example shown in figure 4 of the paper can be obtained by running the simulation as described above and then by double clicking on the filename '.\main\RunExampleFig.m' into matlab. Click on "run" and wait for a couple of minutes until the results are displayed. Original figure Url: <a href="http://www.frontiersin.org/files/Articles/156944/fncom-09-00141-HTML/image_m/fncom-09-00141-g004.jpg">http://www.frontiersin.org/files/Articles/156944/fncom-09-00141-HTML/image_m/fncom-09-00141-g004.jpg</a> As stated in the orginal figure's caption, 'Shown are raster diagram of cell firing (A), firing-rate histogram with interpolated spline polynomial (B), wavelet transform (C) and Fourier transform (D) of the excitatory population. The cells fired at a frequency of about 10 Hz. Note that due to the highly synchronized activity, the Fourier transform (D) also produced a peak at a harmonic frequency (about 20 Hz), but there were no cells that actually fired at that frequency [see (A)]. There are large fluctuations in oscillation amplitude (B) that occasionally just drop below the HAE threshold. Cells had h-channels but did not receive CDC or AP input.' Manipulating and Changing parameters: To change connection probabilities, synaptic strength, and characteristics of the input, such as interspike intervals and CDC (current) amplitudes, edit the file \main\functions_net_bgk_multitest_sparse.hoc and check for the respective parameter in lines 7-33 in file. To change the output file, open the folder \main\sessions and load the file "DrivePower_run_mono_no_spk.ses" and modify the content of line 41 file_name="./output_matlab/WaxingWaning" with the modified name. Finally, in order to add or remove H-channels, go to the templates folder and use your favorite editor to open: FS_WT_modif.tem Pyram_WT_modif.tem and comment in each file, the lines with the next content: =================================== //h-currents insert htc ehd_htc=-30 //(mV) ghdbar_htc=(5)*1e-5 =================================== Additional References: Chen, K., Aradi, I., Thon, N., Eghbal-Ahmadi, M., Baram, T. Z., and Soltesz, I. (2001). Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability. Nat. Med. 7, 331-337. doi: <a href="http://dx.doi.org/10.1038/85480">10.1038/85480</a> Biel, M., Wahl-Schott, C., Michalakis, S., and Zong, X. (2009). Hyperpolarization-activated cation channels: from genes to function. Physiol. Rev. 89, 847-885. doi: <a href="http://dx.doi.org/10.1152/physrev.00029.2008">10.1152/physrev.00029.2008</a> </pre></html>