Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids.
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.
uOttawa, Brain and Mind Research Institute Centre for Neural Dynamics, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada K1G 5Z3; Neuroscience Graduate Program, University of Ottawa, Ottawa, ON, Canada K1H 8M5;
Sean D
SD
Geddes
uOttawa, Brain and Mind Research Institute Centre for Neural Dynamics, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5; Neuroscience Graduate Program, University of Ottawa, Ottawa, ON, Canada K1H 8M5;
Saleha
S
Assadzada
uOttawa, Brain and Mind Research Institute Centre for Neural Dynamics, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada K1G 5Z3;
David
D
Lemelin
Ottawa Hospital Research Institute, Ottawa, ON, Canada K1Y 4E9;
Alexandra
A
Sokolovski
Ottawa Hospital Research Institute, Ottawa, ON, Canada K1Y 4E9;
Richard
R
Bergeron
Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203; Department of Pharmacology, University at Buffalo, Buffalo, NY 14203.
Samir
S
Haj-Dahmane
uOttawa, Brain and Mind Research Institute Centre for Neural Dynamics, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada K1G 5Z3; Neuroscience Graduate Program, University of Ottawa, Ottawa, ON, Canada K1H 8M5; jbeique@uottawa.ca.
Jean-Claude
JC
Béïque
D000818:Animals; D002186:Cannabinoids / Q000378:metabolism*; D065847:Dorsal Raphe Nucleus / Q000502:physiology*; D059330:GABAergic Neurons / Q000378:metabolism*; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000378:metabolism*
D002186:Cannabinoids
anxiety; depression; glutamate receptors; optogenetics; synapse