Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist D-serine

Dallérac, Glenn; Li, Xia; Lecouflet, Pierre; Morisot, Nadège; Sacchi, Silvia; Asselot, Rachel; Pham, Thu Ha; Potier, Brigitte; Watson, David J. G.; Schmidt, Staffan; Levasseur, Grégoire; Fossat, Pascal; Besedin, Andrey; Rivet, Jean Michel; Coyle, Joseph T.; Collo, Ginetta; Pollegioni, Loredano; Kehr, Jan; Galante, Micaela; Fone, Kevin C.; Gardier, Alain M.; Freret, Thomas; Contarino, Angelo; Millan, Mark J.; Mothet, Jean Pierre

Abstract

Prefrontal control of cognitive functions critically depends upon glutamatergic transmission and N-methyl D-aspartate (NMDA) receptors, the activity of which is regulated by dopamine. Yet whether the NMDA receptor coagonist D-serine is implicated in the dopamine-glutamate dialogue in the prefrontal cortex (PFC) and other brain areas remains unexplored. Here, using electrophysiological recordings, we show that D-serine is required for the fine-tuning of glutamatergic neurotransmission, neuronal excitability, and synaptic plasticity in the PFC through the actions of dopamine at D1 and D3 receptors. Using in vivo microdialysis, we show that D1 and D3 receptors exert a respective facilitatory and inhibitory influence on extracellular levels and activity of D-serine in the PFC, with actions expressed primarily via the cAMP/protein kinase A (PKA) signaling cascade. Further, using functional magnetic resonance imaging (fMRI) and behavioral assessment, we show that D-serine is required for the potentiation of cognition by D3R blockade as revealed in a test of novel object recognition memory. Collectively, these results unveil a key role for D-serine in the dopaminergic neuromodulation of glutamatergic transmission and PFC activity, findings with clear relevance to the pathogenesis and treatment of diverse brain disorders involving alterations in dopamine-glutamate cross-talk.

Citation

Dallérac, G., Li, X., Lecouflet, P., Morisot, N., Sacchi, S., Asselot, R., …Mothet, J. P. (2021). Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist D-serine. Proceedings of the National Academy of Sciences, 118(23), Article e2023750118. https://doi.org/10.1073/pnas.2023750118

• Journal Article Type: Article
• Acceptance Date: May 3, 2021
• Online Publication Date: Jun 3, 2021
• Publication Date: Jun 8, 2021
• Deposit Date: Jul 5, 2021
• Publicly Available Date: Dec 4, 2021
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Print ISSN: 0027-8424
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 118
• Issue: 23
• Article Number: e2023750118
• DOI: https://doi.org/10.1073/pnas.2023750118
• Keywords: Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/5633395
• Publisher URL: https://www.pnas.org/content/118/23/e2023750118