Models that contain the Model Concept : Neurotransmitter dynamics

(These models include properties that regulate the flow of ions such as calcium which in turn control the rate of release of neurotransmitters. These properties can include buffers inside and outside the cell, and ion pumps and channels in the plasma membrane or sarcoplasmic or endoplasmic reticulum.)
Re-display model names without descriptions
    Models   Description
1.  Cerebellar Golgi cells, dendritic processing, and synaptic plasticity (Masoli et al 2020)
The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. To study the mechanisms through which these neurons integrate complex input patterns, a new set of models were developed using the latest experimental information and a genetic algorithm approach to fit the maximum ionic channel conductances. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons.
2.  Conductance based model for short term plasticity at CA3-CA1 synapses (Mukunda & Narayanan 2017)
We develop a new biophysically rooted, physiologically constrained conductance-based synaptic model to mechanistically account for short-term facilitation and depression, respectively through residual calcium and transmitter depletion kinetics. The model exhibits different synaptic filtering profiles upon changing certain parameters in the base model. We show degenercy in achieving similar plasticity profiles with different presynaptic parameters. Finally, by virtually knocking out certain conductances, we show the differential contribution of conductances.
3.  Multiscale model of excitotoxicity in PD (Muddapu and Chakravarthy 2020)
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc). Although the exact cause of cell death is not clear, the hypothesis that metabolic deficiency is a key factor has been gaining attention in recent years. In the present study, we investigate this hypothesis using a multi-scale computational model of the subsystem of the basal ganglia comprising Subthalamic Nucleus (STN), Globus Pallidus externa (GPe) and SNc. The proposed model is a multiscale model in that interactions among the three nuclei are simulated using more abstract Izhikevich neuron models, while the molecular pathways involved in cell death of SNc neurons are simulated in terms of detailed chemical kinetics. Simulation results obtained from the proposed model showed that energy deficiencies occurring at cellular and network levels could precipitate the excitotoxic loss of SNc neurons in PD. At the subcellular level, the models show how calcium elevation leads to apoptosis of SNc neurons. The therapeutic effects of several neuroprotective interventions are also simulated in the model. From neuroprotective studies, it was clear that glutamate inhibition and apoptotic signal blocker therapies were able to halt the progression of SNc cell loss when compared to other therapeutic interventions, which only slows down the progression of SNc cell loss.
4.  Single-cell comprehensive biophysical model of SN pars compacta (Muddapu & Chakravarthy 2021)
Parkinson’s disease (PD) is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We hypothesize that “Energy deficiency at a sub-cellular/cellular/systems-level can be a common underlying cause for SNc cell loss in PD.” Here, we propose a comprehensive computational model of SNc cell which helps us to understand the pathophysiology of neurodegeneration at subcellular-level in PD. We were able to show see how deficits in supply of energy substrates (glucose and oxygen) lead to a deficit in ATP, and furthermore, deficits in ATP are the common factor underlying the pathological molecular-level changes including alpha-synuclein aggregation, ROS formation, calcium elevation, and dopamine dysfunction. The model also suggests that hypoglycemia plays a more crucial role in leading to ATP deficits than hypoxia. We believe that the proposed model provides an integrated modelling framework to understand the neurodegenerative processes underlying PD.

Re-display model names without descriptions