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

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.

Altered synaptic plasticity at hippocampal CA1–CA3 synapses in Alzheimer's disease: integration of amyloid precursor protein intracellular domain and amyloid beta effects into computational models

“…We extended the Glu2NB-NMDAR and Glu2NA-NMDAR subunit-dependent voltage-based model of synaptic plasticity at hippocampal CA3-CA1 synapses (Dainauskas et al, 2023 ) to analyse the effects of elevated levels of two AID peptides, AICD and oligomeric A β , and modeled synaptic modifications in a cluster of synapses distributed on the proximal apical dendrites of a detailed compartmental model of a CA1 pyramidal neuron. We optimized the ion channels of the CA1 pyramidal neuron model to account for reduced intrinsic excitability in AICD conditions (Pousinha et al, 2019 ).…”

“…We used a modified NMDAR subunit-dependent voltage-based model of synaptic weight change at hippocampal CA3–CA1 synapses (Dainauskas et al, 2023 ) to investigate the effect of elevated levels of A β and AICD. We embedded this model into a multicompartmental CA1 pyramidal neuron model (Peng et al, 2016 ; Migliore et al, 2018 ) to study the influence of AICD and of A β on synaptic weights within a cluster of randomly distributed CA3–CA1 synapses onto apical dendrites of a CA1 neuron in the stratum radiatum (SR) region.…”

“…We employed a phenomenological voltage-dependent NMDAR-based synaptic plasticity model, developed in our previous study (Dainauskas et al, 2023 ) (ModelDB accession number 267680), and extended it to incorporate the effects of AICD and A β in AD. The model relies on the functioning of the GluN2A-NMDAR and GluN2B-NMDAR subunits as the separate mediators of LTD and LTP, respectively.…”