Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist <scp>d</scp> -serine
Glenn Dallérac, Xia Li, Pierre Lecouflet, Nadège Morisot, Silvia Sacchi, Rachel Asselot, Thu Ha Pham, Brigitte Potier, David J. Watson, Staffan Schmidt, Grégoire Levasseur, Pascal Fossat, A. G. Besedin, Jean‐Michel Rivet, Joseph T. Coyle, Ginetta Collo, Loredano Pollegioni, Ján Kehr, Micaela Galante, K.C.F. Fone, Alain M. Gardier, Thomas Fréret, Angelo Contarino, Mark J. Millan, Jean‐Pierre Mothet
Abstract
Significance Dopamine and glutamate in the prefrontal cortex are important substrates of higher cognitive functions, which are impaired in neuropsychiatric disorders. As regards glutamatergic pathways, a role for the NMDA receptor coagonist d -serine has been highlighted, yet its relationship to dopaminergic transmission remains unclear. In this study, we reveal that d -serine plays a pivotal role in the modulation by dopamine of NMDA receptor activity and cognitive performance in the prefrontal cortex. Comprehensive evidence for this interaction is provided at the synaptic, neuronal, network, and behavioral levels. These observations are of relevance to the pathophysiology and treatment of cognitive impairment in numerous disorders involving disruption of the frontocortical dialogue between dopamine and glutamate.