title: Localization and function of the cannabinoid CB1 receptor in the anterolateral bed nucleus of the stria terminalis.
abstract: BACKGROUND
  The bed nucleus of the stria terminalis (BNST) is involved in behaviors related to natural reward, drug addiction and stress. In spite of the emerging role of the endogenous cannabinoid (eCB) system in these behaviors, little is known about the anatomy and function of this system in the anterolateral BNST (alBNST). The aim of this study was to provide a detailed morphological characterization of the localization of the cannabinoid 1 (CB1) receptor a necessary step toward a better understanding of the physiological roles of the eCB system in this region of the brain.
  
  
  RESULTS
  We have combined anatomical approaches at the confocal and electron microscopy level to ex-vivo electrophysiological techniques. Here, we report that CB1 is localized on presynaptic membranes of about 55% of immunopositive synaptic terminals for the vesicular glutamate transporter 1 (vGluT1), which contain abundant spherical, clear synaptic vesicles and make asymmetrical synapses with alBNST neurons. About 64% of vGluT1 immunonegative synaptic terminals show CB1 immunolabeling. Furthermore, 30% and 35% of presynaptic boutons localize CB1 in alBNST of conditional mutant mice lacking CB1 mainly from GABAergic neurons (GABA-CB1-KO mice) and mainly from cortical glutamatergic neurons (Glu-CB1-KO mice), respectively. Extracellular field recordings and whole cell patch clamp in the alBNST rat brain slice preparation revealed that activation of CB1 strongly inhibits excitatory and inhibitory synaptic transmission.
  
  
  CONCLUSIONS
  This study supports the anterolateral BNST as a potential neuronal substrate of the effects of cannabinoids on stress-related behaviors.
authors.affiliation: Department of Neurosciences, Faculty of Medicine and Dentistry, Basque Country University, Bilbao, Spain.
authors.forename: Nagore
authors.initials: N
authors.lastname: Puente
authors.forename: Izaskun
authors.initials: I
authors.lastname: Elezgarai
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lafourcade
authors.forename: Leire
authors.initials: L
authors.lastname: Reguero
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: François
authors.initials: F
authors.lastname: Georges
authors.forename: Olivier J
authors.initials: OJ
authors.lastname: Manzoni
authors.forename: Pedro
authors.initials: P
authors.lastname: Grandes
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012686:Septal Nuclei / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid