Brief exposure to enriched environment rapidly shapes the glutamate synapse in the rat brain: a metaplastic fingerprint

Abstract

Abstract Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its complexity, the underling mechanisms are not yet fully elucidated. Recent evidence suggests that EE, acting as a metaplastic agent, may affect glutamatergic mechanisms underlying appetitive memory and in turn, modulate reward-seeking behaviors. Here, we explore the hypothetical metaplastic effects induced by brief EE exposure on glutamatergic transmission in brain areas involved in rewarding and memory processes. Adult male Sprague-Dawley rats were exposed to EE for 22h and the expression of critical elements of the glutamate synapse were measured 2h after the end of EE in medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp). We focused our attention on the expression of NMDA and AMPA receptor subunits, their scaffolding proteins SAP102 and SAP97, vesicular and membrane glutamate transporters vGluT1 and GLT-1, and critical structural components such as proteins involved in morphology and function of glutamatergic synapses, PSD95 and Arc/Arg3.1. Our findings demonstrate that a brief EE exposure induces metaplastic changes on glutamatergic mPFC-NAc-Hipp brain areas, which are critical for reward and learning processes. Such changes were area-specific and involved a rearrangement of postsynaptic NMDA/AMPA receptor subunit composition, as well as changes in the expression of their main scaffolding proteins thus influencing the retention of such receptors at synaptic sites. Our data indicate that brief EE exposure is sufficient to cause metaplastic activity at glutamatergic synapses in mPFC-NAc-Hipp circuits, which may modulate several mental processes such as rewarding, learning and memory processes.