Models that contain the Implementer : Diwakar, Shyam [shyam at]

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    Models   Description
1.  A systems model of Parkinson’s disease using biochemical systems theory (Sasidharakurup et al. 2017)
Major pathways involving in Parkinson's disease (PD) such as alphasynuclein aggregation, dopamine synthesis, lewy body formation, tau phosphorylation, parkin, and apoptosis were modeled using stochastic differential equations. Pathways were modeled and simulated using the biochemical pathway visualization program CellDesigner, a modeling tool for gene-regulatory and biochemical networks that support graphical notation and listing of symbols. The model allows a qualitative analysis of PD and a key signalling pathways for evaluating PD treatment conditions relating pathophysiology to molecular concentration changes recorded in experiments.
2.  Computational Modelling of TNFalpha Pathway in Parkinson's Disease (Sasidharakurup et al 2019)
"The paper aims developing a computational framework of signaling using the principles of biochemical systems theory as a model for Parkinson’s disease. Several molecular interactions aided by TNFalpha, a proinflammatory cytokine play key roles in mediating glutamate excitotoxicity and neuroinflammation, resulting in neuronal cell death. In this paper, initial concentrations and rate constants were extracted from literature and simulations developed were based on systems of ordinary differential equations following first-order kinetics. In control or healthy conditions, a decrease in TNFalpha and neuronal cell death was predicted in simulations matching data from experiments, whereas in diseased condition, a drastic increase in levels of TNFalpha, glutamate, TNFR1 and ROS were observed similar to experimental data correlating diseased condition to augmented neuronal cell death. The study suggests toxic effects induced by TNFalpha in the substantia nigra may be attributed to Parkinson’s disease conditions."
3.  Modeling single neuron LFPs and extracellular potentials with LFPsim (Parasuram et al. 2016)
LFPsim - Simulation scripts to compute Local Field Potentials (LFP) from cable compartmental models of neurons and networks implemented in the NEURON simulation environment.
4.  Multicompartmental cerebellar granule cell model (Diwakar et al. 2009)
A detailed multicompartmental model was used to study neuronal electroresponsiveness of cerebellar granule cells in rats. Here we show that, in cerebellar granule cells, Na+ channels are enriched in the axon, especially in the hillock, but almost absent from soma and dendrites. Numerical simulations indicated that granule cells have a compact electrotonic structure allowing EPSPs to diffuse with little attenuation from dendrites to axon. The spike arose almost simultaneously along the whole axonal ascending branch and invaded the hillock, whose activation promoted spike back-propagation with marginal delay (<200 micros) and attenuation (<20 mV) into the somato-dendritic compartment. For details check the cited article.
5.  Reconstructing cerebellar granule layer evoked LFP using convolution (ReConv) (Diwakar et al. 2011)
The model allows reconstruction of evoked local field potentials as seen in the cerebellar granular layer. The approach uses a detailed model of cerebellar granule neuron to generate data traces and then uses a "ReConv" or jittered repetitive convolution technique to reproduce post-synaptic local field potentials in the granular layer. The algorithm was used to generate both in vitro and in vivo evoked LFP and reflected the changes seen during LTP and LTD, when such changes were induced in the underlying neurons by modulating release probability of synapses and sodium channel regulated intrinsic excitability of the cells.

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