Brief exposure to enriched environment rapidly shapes the glutamate synapses in the rat brain: A metaplastic fingerprint

• Published in: The European journal of neuroscience 2024-03, Vol.59 (5), p.982-995
• Main Authors: Pintori, Nicholas, Piva, Alessandro, Mottarlini, Francesca, Díaz, Fernando Castillo, Maggi, Coralie, Caffino, Lucia, Fumagalli, Fabio, Chiamulera, Cristiano
• Format: Article
• Language: English
• Subjects: Addictions; Enrichment; environmental enrichment; glutamatergic synapses; Glutamatergic transmission; Glutamic acid receptors (ionotropic); learning; memory; metaplasticity; N-Methyl-D-aspartic acid receptors; Nucleus accumbens; Postsynaptic density proteins; Prefrontal cortex; Proteins; reward; Subunit structure; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.16279

Environmental enrichment (EE) has been shown to produce beneficial effects in addiction disorders; however, due to its configurational complexity, the underlying 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 behaviours: here, we have investigated such a possibility following a brief EE exposure. Adult male Sprague–Dawley rats were exposed to EE for 22 h and the expression of critical elements of the glutamate synapse was measured 2 h after the end of EE in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (Hipp) brain areas, which are critical for reward and memory. We focused our investigation 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 in glutamatergic mPFC, NAc and Hipp. Such changes are area‐specific and involve 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 dynamically modulate the glutamatergic synapses in mPFC‐NAc‐Hipp circuits, which may modulate rewarding and memory processes. 22 h exposure to an enriched environment (EE) dynamically modulates postsynaptic NMDA and AMPA receptor subunit composition as well as their specific scaffolding protein in rat mPFC, NAc, and Hipp. These brain region‐specific events represent metaplastic mechanisms to prime the glutamatergic synapses to subsequent experiences.