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TitleTarget-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids.
Publication TypeJournal Article
Year of Publication2016
AuthorsGeddes, Sean D., Saleha Assadzada, David Lemelin, Alexandra Sokolovski, Richard Bergeron, Samir Haj-Dahmane, and Jean-Claude Béïque
JournalProc Natl Acad Sci U S A
Date Published2016 May 10
KeywordsAnimals, Cannabinoids, Dorsal Raphe Nucleus, GABAergic Neurons, Models, Neurological, Nerve Net, Neural Pathways, Prefrontal Cortex, Rats, Rats, Sprague-Dawley, Serotonergic Neurons

Serotonin (5-HT) neurons located in the raphe nuclei modulate a wide range of behaviors by means of an expansive innervation pattern. In turn, the raphe receives a vast array of synaptic inputs, and a remaining challenge lies in understanding how these individual inputs are organized, processed, and modulated in this nucleus to contribute ultimately to the core coding features of 5-HT neurons. The details of the long-range, top-down control exerted by the medial prefrontal cortex (mPFC) in the dorsal raphe nucleus (DRN) are of particular interest, in part, because of its purported role in stress processing and mood regulation. Here, we found that the mPFC provides a direct monosynaptic, glutamatergic drive to both DRN 5-HT and GABA neurons and that this architecture was conducive to a robust feed-forward inhibition. Remarkably, activation of cannabinoid (CB) receptors differentially modulated the mPFC inputs onto these cell types in the DRN, in effect regulating the synaptic excitatory/inhibitory balance governing the excitability of 5-HT neurons. Thus, the CB system dynamically reconfigures the processing features of the DRN, a mood-related circuit believed to provide a concerted and distributed regulation of the excitability of large ensembles of brain networks.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID27114535
PubMed Central IDPMC4868450