title: Oxytocin activation of neurons in ventral tegmental area and interfascicular nucleus of mouse midbrain.
abstract: Oxytocin (OT) was reported to affect cognitive and emotional behavior by action in ventral tegmental area (VTA) and other brain areas. However, it is still unclear how OT activates VTA and related midline nucleus. Here, using patch-clamp recording, we studied the effects of OT on neuron activity in VTA and interfascicular nucleus (IF). OT dose-dependently and selectively excited small neurons located in medial VTA and the majority of IF neurons but not large neurons in lateral VTA. We found the hyperpolarization-activated current (I(h)) and the membrane capacitance of OT-sensitive neuron were significantly smaller than those of OT-insensitive neurons. The action potential width of OT-sensitive neurons was about half that of OT-insensitive neurons. The OT effect was blocked by the OT receptor antagonist atosiban and WAY-267464 but not by tetrodotoxin, suggesting a direct postsynaptic activation of OT receptors. In addition, the phospholipase C (PLC) inhibitor U73122 antagonized the depolarization by OT. Both the nonselective cation channel (NSCC) antagonist SKF96365 and the Na(+)-Ca(2+) exchanger (NCX) blocker SN-6 attenuated OT effects. These results suggested that the PLC signaling pathway coupling to NSCC and NCX contributes to the OT-mediated activation of neurons in medial VTA and IF. Taken together, our results indicate OT directly acted on medial VTA and especially IF neurons to activate NSCC and NCX via PLC. The direct activation by OT of midbrain neurons may be one mechanism underlying OT effects on social behavior.
authors.affiliation: Department of Laboratory, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Huai
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Laboratory, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Cunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha 410011, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Laboratory, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Tang
authors.affiliation: Mental Health Institute, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha 410011, China. Electronic address: csuliuyong@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008636:Mesencephalon / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011720:Pyrazoles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: C547280:4-(3,5-dihydroxybenzyl)-N-(2-methyl-4-((1-methyl-4,10-dihydropyrazolo(3,4-b)(1,5)benzodiazepin-5(1H)-yl)carbonyl)benzyl)piperazine-1-carboxamide; D011720:Pyrazoles; C047046:atosiban; D001569:Benzodiazepines; D010121:Oxytocin; D014668:Vasotocin
keywords: I(h); IF; Interfascicular nucleus; NCX; NSCC; Na(+)–Ca(2+) exchanger; OT; OTR; Oxytocin; PFC; PLC; VTA; Vasopressin; Ventral tegmental area; hyperpolarization-activated current; interfascicular nucleus; nonselective cation channel; oxytocin; oxytocin receptor; phospholipase C; prefrontal cortex; ventral tegmental area