ArticlePloS one2023
Dorsal raphe stimulation relays a reward signal to the ventral tegmental area via GluN2C NMDA receptors.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 2 citations in OpenAlex.
- Neuronal Grin2c expression and the cocaine engram: a medial prefrontal cortex substrate for conditioned place preference.bioRxiv : the preprint server for biology · 2026Article
- Serotonergic regulation of the dopaminergic system: Implications for reward-related functions.Neuroscience and biobehavioral reviews · 2021Review
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6 authors at 1 institution in 1 country.
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Abstract
backgroundGlutamate relays a reward signal from the dorsal raphe (DR) to the ventral tegmental area (VTA). However, the role of the different subtypes of N-methyl-D-aspartate (NMDA) receptors is complex and not clearly understood. Therefore, we measured NMDA receptors subunits expression in limbic brain areas. In addition, we studied the effects of VTA down-regulation of GluN2C NMDA receptor on the reward signal that arises from DR electrical stimulation.
methodsUsing qPCR, we identified the relative composition of the different Grin2a-d subunits of the NMDA receptors in several brain areas. Then, we used fluorescent in situ hybridization (FISH) to evaluate the colocalization of Grin2c and tyrosine hydroxylase (TH) mRNA in VTA neurons. To assess the role of GluN2C in brain stimulation reward, we downregulated this receptor using small interfering RNA (siRNA) in rats self-stimulating for electrical pulses delivered to the DR. To delineate further the specific role of GluN2C in relaying the reward signal, we pharmacologically altered the function of VTA NMDA receptors by bilaterally microinjecting the NMDA receptor antagonist PPPA.
resultsWe identified GluN2C as the most abundant subunit of the NMDA receptor expressed in the VTA. FISH revealed that about 50% of TH-positive neurons colocalize with Grin2c transcript. siRNA manipulation produced a selective down-regulation of the GluN2C protein subunit and a significant reduction in brain stimulation reward. Interestingly, PPPA enhanced brain stimulation reward, but only in rats that received the nonactive RNA sequence.
conclusionThe present results suggest that VTA glutamate neurotransmission relays a reward signal initiated by DR stimulation by acting on GluN2C NMDA receptors.
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