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While existing models of AMPA and NMDA receptor kinetics often oversimplify glutamate dynamics or become computationally intractable, this study develops a balanced, biophysically grounded model that integrates glutamate transport, receptor sensitivity, and electrotonic effects. Using rat hippocampal slices, we recorded postsynaptic currents in CA1 pyramidal neurons under control conditions and during glutamate transporter blockade. The proposed mathematical model, formulated as a system of seven ordinary differential equations, distinguishes somatic and dendritic compartments, synaptic plasticity, and differential glutamate sensitivity of AMPA and NMDA receptors. Key findings reveal that the glutamate transporter blockade prolongs NMDA receptor-mediated currents without altering AMPA receptor kinetics, consistent with the higher glutamate sensitivity of NMDA receptors. The model also predicts glutamate concentrations in synaptic and extrasynaptic spaces, offering insights into spatial neurotransmitter dynamics. Furthermore, it accounts for voltage-dependent NMDA responses and short-term plasticity observed experimentally. By bridging the gap between oversimplified and overly complex approaches, this work provides a versatile tool for studying synaptic transmission in normal and pathological conditions, such as epilepsy or neurodegenerative diseases, where glutamate dysregulation plays a central role.<\/jats:p>","DOI":"10.1007\/s10827-026-00935-8","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T10:00:50Z","timestamp":1778666450000},"page":"393-406","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A biophysically grounded model of glutamatergic synaptic transmission integrating glutamate transport, receptor kinetics, and electrotonic effects"],"prefix":"10.1007","volume":"54","author":[{"given":"A. V.","family":"Chizhov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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