GluN2B-NMDAR subunit contribution on synaptic plasticity: A phenomenological model for CA3-CA1 synapses

Justinas J Dainauskas; Hélène Marie; Michele Migliore; Ausra Saudargiene

doi:10.3389/fnsyn.2023.1113957

GluN2B-NMDAR subunit contribution on synaptic plasticity: A phenomenological model for CA3-CA1 synapses

Front Synaptic Neurosci. 2023 Mar 15:15:1113957. doi: 10.3389/fnsyn.2023.1113957. eCollection 2023.

Authors

Justinas J Dainauskas^{1

2}, Hélène Marie³, Michele Migliore⁴, Ausra Saudargiene¹

Affiliations

¹ Laboratory of Biophysics and Bioinformatics, Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania.
² Department of Informatics, Vytautas Magnus University, Kaunas, Lithuania.
³ Université Côte d'Azur, Centre National de la Recherche Scientifique (CNRS) UMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Valbonne, France.
⁴ Institute of Biophysics, National Research Council, Palermo, Italy.

Abstract

Synaptic plasticity is believed to be a key mechanism underlying learning and memory. We developed a phenomenological N-methyl-D-aspartate (NMDA) receptor-based voltage-dependent synaptic plasticity model for synaptic modifications at hippocampal CA3-CA1 synapses on a hippocampal CA1 pyramidal neuron. The model incorporates the GluN2A-NMDA and GluN2B-NMDA receptor subunit-based functions and accounts for the synaptic strength dependence on the postsynaptic NMDA receptor composition and functioning without explicitly modeling the NMDA receptor-mediated intracellular calcium, a local trigger of synaptic plasticity. We embedded the model into a two-compartmental model of a hippocampal CA1 pyramidal cell and validated it against experimental data of spike-timing-dependent synaptic plasticity (STDP), high and low-frequency stimulation. The developed model predicts altered learning rules in synapses formed on the apical dendrites of the detailed compartmental model of CA1 pyramidal neuron in the presence of the GluN2B-NMDA receptor hypofunction and can be used in hippocampal networks to model learning in health and disease.

Keywords: CA1 pyramidal neuron; GluN2B-NMDA receptor subunit; NMDA receptor; hippocampus; synaptic plasticity.

Grants and funding

This research was funded by the Research Council of (Lithuania), Agence Nationale de la Recherche (France) (Flagship ERA-NET Joint Transnational Call JTC 2019 in synergy with the Human Brain Project, No. S-FLAG-ERA-20-1/2020-PRO-28), the EU Horizon 2020 Framework Program for Research and Innovation (Specific Grant 945539, Human Brain Project SGA3), Fenix computing and storage resources was provided under Specific Grant Agreement No. 800858 (Human Brain Project ICEI), and a grant from the Swiss National Supercomputing Centre (CSCS) under project ID ich011. MM also acknowledges a contribution from the Italian National Recovery and Resilience Plan (NRRP), M4C2 and funded by the European Union - NextGenerationEU (Project IR0000011, CUP B51E22000150006, EBRAINS-Italy.