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Models that contain the Implementer : Korngreen, Alon [alon.korngreen at gmail.com]

   Models   Description
Ion channel modeling with whole cell and a genetic algorithm (Gurkiewicz and Korngreen 2007)
"... Here we show that a genetic search algorithm in combination with a gradient descent algorithm can be used to fit whole-cell voltage-clamp data to kinetic models with a high degree of accuracy. Previously, ion channel stimulation traces were analyzed one at a time, the results of these analyses being combined to produce a picture of channel kinetics. Here the entire set of traces from all stimulation protocols are analysed simultaneously. The algorithm was initially tested on simulated current traces produced by several Hodgkin-Huxley–like and Markov chain models of voltage-gated potassium and sodium channels. ... Finally, the algorithm was used for finding the kinetic parameters of several voltage-gated sodium and potassium channels models by matching its results to data recorded from layer 5 pyramidal neurons of the rat cortex in the nucleated outside-out patch configuration. The minimization scheme gives electrophysiologists a tool for reproducing and simulating voltage-gated ion channel kinetics at the cellular level."
Mechanisms of magnetic stimulation of central nervous system neurons (Pashut et al. 2011)
Transcranial magnetic stimulation (TMS) is a widely applied tool for probing cognitive function in humans and is one of the best tools for clinical treatments and interfering with cognitive tasks. Surprisingly, while TMS has been commercially available for decades, the cellular mechanisms underlying magnetic stimulation remain unclear. Here we investigate these mechanisms using compartmental modeling. We generated a numerical scheme allowing simulation of the physiological response to magnetic stimulation of neurons with arbitrary morphologies and active properties. Computational experiments using this scheme suggested that TMS affects neurons in the central nervous system (CNS) primarily by somatic stimulation.
Space clamp problems in neurons with voltage-gated conductances (Bar-Yehuda and Korngreen 2008)
" ... using numerical simulations, we show that the distortions of voltage-gated K+ and Ca2+ currents are substantial even in neurons with short dendrites. The simulations also demonstrate that passive cable theory cannot be used to justify voltage-clamping of neurons, due to significant shunting to the reversal potential of the voltage-gated conductance during channel activation. ... "
Subthreshold inact. of K channels modulates APs in bitufted interneurons (Korngreen et al 2005)
... In this study we show that in bitufted interneurones from layer 2/3 of the somatosensory cortex, the height and width of APs recorded at the soma are sensitive to changes in the resting membrane potential, suggesting subthreshold activity of voltage-gated conductances. Attributes of K+ currents examined in nucleated patches revealed a fast subthreshold-inactivating K+ conductance (Kf ) and a slow suprathreshold-inactivating K+ conductance (Ks ). Simulations of these K+ conductances, incorporated into a Hodgkin–Huxley-type model, suggested that during a single AP or during low frequency trains of APs, subthreshold inactivation of Kf was the primary modulator of AP shape, whereas during trains of APs the shape was governed to a larger degree by Ks resulting in the generation of smaller and broader APs. ... Compartmental simulation of the back-propagating AP suggested a mechanism for the modulation of the back-propagating AP height and width by subthreshold activation of Kf . We speculate that this signal may modulate retrograde GABA release and consequently depression of synaptic efficacy of excitatory input from neighbouring pyramidal neurones.


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