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Paradoxical effect of fAHP amplitude on gain in dentate gyrus granule cells (Jaffe & Brenner 2018)
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<html> <hr/> Paradoxical role gain-of-function BK channels: effect of fAHP <hr/> <p>Title: A computational model for how the fast afterhyperpolarization paradoxically increases gain in regularly firing neurons <p/> Jaffe, D.B. and Brenner R*. </p> <p>Department of Biology, UTSA Neurosciences Institute, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA. *Department of Cell and Integrative Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. </p> <p>J. Neurophysiology </p> <p>The afterhyperpolarization (AHP) is canonically viewed as a major factor underlying the refractory period, serving to limit neuronal firing rate. We recently reported (Wang et al, J. Neurophys. 116:456, 2016) that enhancing the amplitude of the fast AHP in a relatively slowly firing neuron (versus fast spiking neurons), augments neuronal excitability in dentate gyrus granule neurons expressing gain-of-function BK channels. Here we present a novel, quantitative hypothesis for how varying the amplitude of the fast AHP (fAHP) can, paradoxically, influence a subsequent spike tens of milliseconds later. </p> <hr/> Simulation <hr/> <p>Reproduces Figure2C1 using Neuron (<a href="https://neuron.yale.edu/neuron/">https://neuron.yale.edu/neuron/</a>) </p> <hr/> Files <hr/> <ul> <li/>Fig2.hoc - Main simulation script <li/>6018866b.nrn - Dentate gyrus granule cell morphology (Claiborne lab) <li/>PlotFig2.py - Python script to plot simulation output (imports csv, matplotlib and numpy) <li/>mods/afKDR.mod - fast KDR - Aradi and Holmes, 1999 <li/>mods/asKDR.mod - slow KDR - Aradi and Holmes, 1999 <li/>mods/DGCaT.mod - T-type Ca channel - Huguenard and McCormick, 1992; Mainen and Sejnowski, 1996 <li/>mods/migNa.mod - Na channel - Lazarewicz, Migliore, and Ascoli, 2002 </ul></p> <hr/> Installation <hr/> <p>Compile all files in the mods folder to generate special executable. In unix/linux type a command like:<p/> nrnivmodl mods <p>If you need extra help in this above step for your platform, please consult this web page: <a href="https://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.cshtml">https://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.cshtml</a> </p> <hr/> Run simulation <hr/> <p>nrngui Fig2.hoc </p> Takes just a few minutes to run and generates output files 1 through 4. You may need to exit Neuron to have the last output file have its contents flushed to disk. <hr/> Plot output <hr/> <p>python PlotFig2.py</p> You should see graphs of voltage trajectories and this one similar to Fig 2C1 in the paper:<p/> <img src="./screenshot2.png" width="550" alt="screenshot"><p/> </html>
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Paradoxical effect of fAHP amplitude on gain in dentate gyrus granule cells (Jaffe & Brenner 2018)
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