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Brief exposure to enriched environment rapidly shapes the glutamate synapse in the rat brain: a metaplastic fingerprint
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  • Nicholas Pintori,
  • Alessandro Piva,
  • Francesca Mottarlini,
  • Fernando Castillo Díaz,
  • Coralie Maggi,
  • Lucia Caffino,
  • Fabio Fumagalli,
  • Christian Chiamulera
Nicholas Pintori
University of Verona

Corresponding Author:[email protected]

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Alessandro Piva
University of Verona
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Francesca Mottarlini
University of Milan
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Fernando Castillo Díaz
University of Milan
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Coralie Maggi
University of Milan
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Lucia Caffino
University of Milan
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Fabio Fumagalli
University of Milan
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Christian Chiamulera
University of Verona
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Abstract

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 behaviors: here, we have investigated such possibility following a brief EE exposure. Adult male Sprague-Dawley rats were exposed to EE for 22h and the expression of critical elements of the glutamate synapse was measured 2h 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.
06 Jul 2023Submitted to European Journal of Neuroscience
07 Jul 2023Submission Checks Completed
07 Jul 2023Assigned to Editor
07 Jul 2023Review(s) Completed, Editorial Evaluation Pending
07 Aug 2023Reviewer(s) Assigned
13 Sep 2023Editorial Decision: Revise Major
22 Sep 20231st Revision Received
25 Sep 2023Submission Checks Completed
25 Sep 2023Assigned to Editor
25 Sep 2023Review(s) Completed, Editorial Evaluation Pending
25 Sep 2023Reviewer(s) Assigned