Role of NMDAR plasticity in a computational model of synaptic memory

Abstract

A largely unexplored question in neuronal plasticity is whether synapses are capable of encoding and learning the timing of synaptic inputs. We address this question in a computational model of synaptic input time difference learning (SITDL), where N‐methyl‐d‐aspartate receptor (NMDAR) isoform expression in silent synapses is affected by time differences between glutamate and voltage signals. We suggest that differences between NMDARs’ glutamate and voltage gate conductances induce modifications of the synapse’s NMDAR isoform population, consequently changing the timing of synaptic response. NMDAR expression at individual synapses can encode the precise time difference between signals. Thus, SITDL enables the learning and reconstruction of signals across multiple synapses of a single neuron. In addition to plausibly predicting the roles of NMDARs in synaptic plasticity, SITDL can be usefully applied in artificial neural network models.

Normal Aging Induces Changes in the Brain and Neurodegeneration Progress: Review of the Structural, Biochemical, Metabolic, Cellular, and Molecular Changes

“…Although NMDARs are non-selective, they are the most permeable to Ca 2+ ion ( Xin et al, 2005 ). NMDAR functions within the brain region decline with aging, including learning and memory ( Gribkova and Gillette, 2021 ). There are several reasons why a decrease in NMDAR function due to aging may occur ( Kumar et al, 2009 ).…”

Computational Modeling of Extrasynaptic NMDA Receptors: Insights into Dendritic Signal Amplification Mechanisms

“…Alongside canonical NR2B, NR2D, and NR2A subunits, NR3A subunits may also be present within these clusters, potentially conferring neuroprotection against excessive calcium influx. Notwithstanding our model's projection of NMDA clusters enriched with subunits featuring prolonged decay kinetics, such as NR2B, it warrants consideration that an altered subunit ratio favoring NR2B could culminate in heightened calcium influx and thereby precipitate excitotoxicity and cell death [66]. Analogously, overstimulation of exNMDA clusters may engender analogous repercussions [62,67].…”

High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats

“…Resting state-fMRI in this study provided indirect evidence that HF-rTMS over the PFC increased neural plasticity in the PFC, hippocampus, M1, and other brain regions, which belong to the interoceptive/DMN and the cortico-striatalthalamic network. A previous study showed that stimulating this region directly excited neurons, and consequently reduced the synaptic conduction threshold, thereby making the synapse become relatively active and increasing the synaptic connections (Gribkova and Gillette, 2021). Several basic studies reported that HF-rTMS improved cognitive function by regulating synaptic plasticity in rodents with cognitive impairment (Zhang et al, 2015;Shang et al, 2019).…”

“…However, it is not clear how rTMS impacts neural plasticity in different brain regions. The NMDA receptors play a central role in synaptic plasticity, which is closely related to learning and memory abilities (Gribkova and Gillette, 2021). Functional NMDA receptors are tetramers composed of different subunits (NR1, NR2A-D, NR3A-B).…”