{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:53Z","timestamp":1788844253053,"version":"build-2803163510"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Comput. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Neuronal firing patterns emerge from complex interactions between intrinsic membrane properties and synaptic receptor dynamics. N-methyl-D-aspartate (NMDA) receptors critically shape calcium influx and synaptic plasticity through their voltage-dependent Mg\n                      <jats:sup>2+<\/jats:sup>\n                      block and prolonged activation kinetics, yet how their closing kinetics interact with glutamatergic drive and GABAergic modulation to control neuronal dynamics and information processing remains incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed a Hodgkin\u2013Huxley-type computational model incorporating NMDA, AMPA, and GABA receptor kinetics to investigate how the NMDA receptor closing rate \u03b2\n                      <jats:sub>\n                        <jats:italic>NMDA<\/jats:italic>\n                      <\/jats:sub>\n                      and glutamatergic stimulation frequency control neuronal dynamics. We performed a systematic analysis of over 2.9 million inter-spike intervals across a large multi-parameter sweep of NMDA kinetics, glutamatergic stimulation frequency, and GABAergic modulation. Dynamical behavior was characterized using entropy\u2013Lyapunov correlation analysis and frequency-dependent bifurcation analysis, and CaMKII phosphorylation was quantified to link kinetic regimes to downstream plasticity signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The analysis revealed two mechanistically distinct pathways to firing irregularity. Pathway 1 (rapid-deactivation irregularity) emerged under relatively fast NMDA deactivation combined with specific input-frequency conditions, producing deterministic chaos with compromised information encoding. Pathway 2 (prolonged-activation irregularity) resulted from slow NMDA deactivation under weak drive, creating irregularity through sustained receptor activation and calcium influx. An optimal kinetic window emerged at \u03b2\n                      <jats:sub>\n                        <jats:italic>NMDA<\/jats:italic>\n                      <\/jats:sub>\n                      = 0.042 ms\n                      <jats:sup>\u22121<\/jats:sup>\n                      , maximizing information transfer (0.275 bits) while maintaining stable dynamics. Entropy\u2013Lyapunov correlation analysis confirmed deterministic chaos, and frequency-dependent bifurcation analysis demonstrated progressive narrowing and displacement of chaotic windows across the analyzed \u03b2\n                      <jats:sub>\n                        <jats:italic>NMDA<\/jats:italic>\n                      <\/jats:sub>\n                      range as stimulation frequency increased. GABAergic inhibition provided frequency-selective stabilization, expanding the stable parameter space by 34.2% while preserving gamma oscillations. CaMKII phosphorylation analysis revealed that prolonged NMDA activation maintained elevated phosphorylation levels, creating conditions for pathological long-term potentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings establish NMDA receptor kinetics as fundamental controllers of cortical excitability and information processing. The dual-pathway framework provides mechanistic insights into addiction-related memory formation, where prolonged NMDA activation enables pathological plasticity, and into visual processing disorders, where altered kinetics disrupt retinal function and cortical oscillatory balance. The identification of optimal kinetic windows and frequency-selective GABA modulation suggests therapeutic strategies based on kinetically specific interventions for neuropsychiatric disorders involving NMDA dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncom.2026.1753444","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:01:34Z","timestamp":1780466494000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["NMDA receptor kinetics drive distinct routes to chaotic firing in pyramidal neurons"],"prefix":"10.3389","volume":"20","author":[{"given":"Mehdi","family":"Borjkhani","sequence":"first","affiliation":[{"name":"International Centre for Translational Eye Research (ICTER), Institute of Physical Chemistry, Polish Academy of Sciences","place":["Warsaw, Poland"]},{"name":"Institute of Physical Chemistry, Polish Academy of Sciences","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi","family":"Borjkhani","sequence":"additional","affiliation":[{"name":"School of Engineering \u2013 Energy and Information, HTW Berlin \u2013 University of Applied Sciences","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morteza A.","family":"Sharif","sequence":"additional","affiliation":[{"name":"Optics and Laser Engineering Group, Faculty of Electrical Engineering, Urmia University of Technology","place":["Urmia, Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariba","family":"Bahrami","sequence":"additional","affiliation":[{"name":"CIPCE, Motor Control and Computational Neuroscience Laboratory, School of ECE, College of Engineering, University of Tehran","place":["Tehran, Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahyar","family":"Janahmadi","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center and Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences","place":["Tehran, Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nrn2356","article-title":"Metaplasticity: tuning synapses and networks for plasticity","volume":"9","author":"Abraham","year":"2008","journal-title":"Nat. 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