Malignant Neuro-Glio-Synaptic Coupling: A Biophysical Framework for Optogenetic Control and Frequency-Dependent Proliferation Mechanics in High-Grade Gliomas

High-grade gliomas do not grow in isolation; they integrate directly into active neural circuits through functional, GluA2-lacking AMPA-receptor-mediated synapses. In this study, we present an ordinary differential equation (ODE) biophysical model evaluating how presynaptic neural firing patterns dictate downstream glioma calcium influx (Ca^2+) and downstream proliferation dynamics. We specifically model and compare 10Hz versus 40Hz optogenetic stimulation regimes across GluA2-lacking AMPA receptor complexes. The computational framework tracks presynaptic glutamate release, postsynaptic membrane depolarization Vm, calcium influx, and downstream pERK/mitogenic pathway activation. To support open science and interactive reproducibility, this model is paired with a live, web-based simulation environment where parameters can be dynamically adjusted in real time. Interactive Web Simulation: https://synapse-mbkzzdbc.manus.space/