Abstract

Activation of N-methyl D-aspartate (NMDA) receptor is important for learning, memory and persistent pain. Genetic enhancement of NMDA receptor function by overexpressing NR2B subunit significantly enhances hippocampal long-term potentiation (LTP), behavioral learning as well as persistent pain. Recent studies found that NMDA NR2B subunits can undergo long-term upregulation in the brain under certain conditions including peripheral injury and environmental enrichment. Considering the fact that laboratory grown animals live in an artificial comfort environment, we wondered if NMDA receptor functions and its related LTP would differ in animals living in a natural wild environment. In this report we performed whole-cell patch-clamp recordings from both laboratory wild-type mice and wild mice from a natural environment. We found that LTP was significantly enhanced in the anterior cingulate cortex (ACC) of the wild mice as compared with that of laboratory mice. In parallel, NMDA receptor NR2B/total NMDA receptor mediated EPSC ratio was significantly increased in slices of wild mice. Our findings provide the first evidence that NMDA NR2B receptors play an important role in experience-dependent synaptic potentiation within the ACC in wild mice as previously reported in laboratory mice.

Highlights

  • The N-methyl D-aspartate (NMDA) receptor plays a critical role in synaptic plasticity in many brain regions including the hippocampus, amygdala and anterior cingulate cortex (ACC) [1]

  • It is known that the NR2A and NR2B subunits predominate in the forebrain neurons, and the NR2A/NR2B subunit composition determines the functional properties of NMDA receptors [3,4]

  • Considering wild mice have developed in a sophisticated city environment, we expect that long-term potentiation (LTP) may be enhanced in the ACC of the wild mice as compared with laboratory mice

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Summary

Introduction

The NMDA receptor plays a critical role in synaptic plasticity in many brain regions including the hippocampus, amygdala and anterior cingulate cortex (ACC) [1]. NMDA receptors are composed of NR1, NR2 (A, B, C, and D), and NR3 (A and B) subunits. The formation of functional NMDA receptors requires a combination of NR1 and at least one NR2 subunit [2]. It is known that the NR2A and NR2B subunits predominate in the forebrain neurons, and the NR2A/NR2B subunit composition determines the functional properties of NMDA receptors [3,4]. NMDA receptor subunits can undergo plastic changes in different regions of the brain during early development and different physiological/ pathological conditions [2,5,6,7,8]. Enriched animals display better leaning, enhanced hippocampal LTP, increased NMDA receptor NR2B subunit mediated currents in the forebrain [9,10]

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