Primate home range and GRIN2A, a receptor gene involved in neuronal plasticity: implications for the evolution of spatial memory

Abstract

N-methyl-D-aspartate (NMDA) glutamate receptors play crucial roles in neuronal synaptic plasticity, learning and memory. However, as to whether different NMDA subunits are implicated in specific forms of memory is unclear. Moreover, nothing is known about the interspecific genetic variability of the GRIN2A subunit and how this variation can potentially explain evolutionary changes in behavioral phenotypes. Here, we used 28 primate GRIN2A sequences and various proxies of memory across primates to investigate the role of GRIN2A. Codon-specific sequence analysis on these sequences showed that GRIN2A in primates coevolved with a likely ecological proxy of spatial memory (relative home-range size) but not with other indices of non-spatial learning and memory such as social memory and social learning. Models based on gene averages failed to detect positive selection in primate branches with major changes in relative home-range size. This implies that accelerated evolution is concentrated in specific parts of the protein expressed by GRIN2A. Overall, our molecular evolution study, the first on GRIN2A, supports the notion that different NMDA subunits may play a role in specific forms of memory and that phenotypic diversity along with genetic evolution can be used to investigate the link between genes and behavior across evolutionary time.

Effect of Acute Stressor and Serotonin Transporter Genotype on Amygdala First Wave Transcriptome in Mice

“…For the first four genes, all involved in calcium signaling, a lack of immediate upregulation was observed compared to stressed WT mice, leading to the assumption of reduced calcium signaling processes. Thereby KO mice might have a reduced ability to adapt to a stressor via neuroplasticity processes as it was supposed above for WTs [44], [47]. Alteration or dysfunction of processes involving plasticity and learning to cope with similar situations in the future might be related to maladaptive reactions and the transition to pathological emotion processing as reviewed recently [52], [53], [54].…”

“…In addition, genes of the functional pathways or clusters calcium signaling and calcium/cation binding like Grin2a, Nr4a2, Nr4a3, Chrm1, Ryr1, Cabp1, or Pvalb were upregulated in acutely stressed WTs . Several of these genes were shown to be related to spatial memory or memory formation (e.g., Grin2a [44], Nr4a2 [45], Ryr1 [46]). Further the calcium signaling pathway on the whole has been implicated in adaptive responses to synaptic activity, synaptic plasticity, and long-lasting changes in synaptic efficacy and memory (recent review by [47]).…”

Molecular evolution of genes in avian genomes

“…GRIN2a encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, a subtype of ionotropic glutamate-gated ion channel that has well-established roles in learning and brain plasticity (reviewed in [86]). A survey of GRIN2a sequences across primate species revealed a specific correlation between ω and home range size, which is taken to be a proxy for spatial memory [87]. Spatial memory is well developed in the songbird (passerine) lineage and is especially evident in food-caching species [88], a behavior that depends on NMDA receptor function [89].…”

Genetic Factors That Could Affect Concussion Risk in Elite Rugby

“…Affects duration of concussion via potential modulation of glutamate-gated ion channel proteins [112][113][114][115].…”

“…A variable number tandem repeat (VNTR) polymorphism within the promoter region of GRIN2A modulates n-methyl-d aspartic acid (NMDA) receptors within the brain. The NMDA NR2A subunit has been associated with neuronal plasticity, spatial and episodic memory [112,113]. The VNTR GT (rs3219790) repeat within the promoter region affects transcriptional activity in a length-dependent manner (Supplementary Figure S6) [114,115].…”