D-serine gets invited to the dopamine-glutamate crosstalks in the prefrontal cortex

Dopamine and D-serine work hand-in-hand to regulate prefrontal cortex activity and plasticity. In a paper published in PNAS, Glenn Dallérac’s team at the Institut des Neurosciences Paris-Saclay – NeuroPSI (CNRS/UPSaclay, Orsay) and Jean-Pierre Mothet’s team at LuMin (UPSaclay/ENS Paris-Saclay/CNRS), shows that dopamine neuromodulations of prefrontal cortex involves the NMDA-receptor co-agonist D-serine. This finding offers a physiological explanation for the beneficial impact of D-serine supplementation in neuropsychiatric disorders associated with dopamine defects. 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 remained unclear. This study reveals 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.

Contact : Glenn Dallérac

Article published in PNASAccess to the manuscript