1. Subcellular specificity of cannabinoid effects in striatonigral circuits
- Author
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Nagore Puente, Ignacio Fernández-Moncada, Yamuna Mariani, Alexander W. Lohman, Luis F. Callado, Francisca Julio-Kalajzić, Tarson Tolentino-Cortes, Massimo Barresi, Arnau Busquets-Garcia, Giovanni Marsicano, Carolina Muguruza, Yasmine Ould Amer, Jérôme Baufreton, Astrid Cannich, Etienne Hebert-Chatelain, Francis Chaouloff, Marjorie Varilh, Tifany Desprez, Luigi Bellocchio, Itziar Bonilla-Del Río, Bastien Redon, Zhe Zhao, Antonio C Pagano Zottola, Laurie M. Robin, Peggy Vincent, José F. Oliveira da Cruz, Pedro Grandes, Morgane Le Bon-Jego, Geoffrey Terral, Robyn Flynn, Julia Goncalves, Gabriel Barreda-Gómez, Jaideep S. Bains, Simone Corinti, Thierry Leste-Lasserre, Edgar Soria-Gomez, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), University of the Basque Country [Bizkaia] (UPV/EHU), Basque Foundation for Science (Ikerbasque), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Calgary, University of Moncton, IMG Pharma Biotech S.L., Biocruces Bizkaia Health Research Institute [Baracaldo], and University of Victoria [Canada] (UVIC)
- Subjects
Male ,Nociception ,0301 basic medicine ,THC ,Cannabinoid receptor ,substance P ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,medicine.medical_treatment ,CB(1) receptor ,Substantia nigra ,Substance P ,Neurotransmission ,Catalepsy ,Synaptic Transmission ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Receptor, Cannabinoid, CB1 ,medicine ,Animals ,Humans ,PKA ,Receptor ,Cannabinoid Receptor Antagonists ,antinociception ,catalepsy ,Cannabinoid Receptor Agonists ,Chemistry ,General Neuroscience ,Cell Membrane ,Brain ,medicine.disease ,Mice, Inbred C57BL ,mitochondria ,HEK293 Cells ,030104 developmental biology ,substantia nigra ,Cannabinoid ,Neuroscience ,030217 neurology & neurosurgery ,HeLa Cells ,Signal Transduction - Abstract
International audience; Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB1) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB1 receptors (pmCB1), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB1 receptors (mtCB1) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB1 receptor signaling within striatonigral circuits determines multimodal control of behavior.
- Published
- 2021
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