title: Pontomesencephalic Tegmental Afferents to VTA Non-dopamine Neurons Are Necessary for Appetitive Pavlovian Learning.
abstract: The ventral tegmental area (VTA) receives phenotypically distinct innervations from the pedunculopontine tegmental nucleus (PPTg). While PPTg-to-VTA inputs are thought to play a critical role in stimulus-reward learning, direct evidence linking PPTg-to-VTA phenotypically distinct inputs in the learning process remains lacking. Here, we used optogenetic approaches to investigate the functional contribution of PPTg excitatory and inhibitory inputs to the VTA in appetitive Pavlovian conditioning. We show that photoinhibition of PPTg-to-VTA cholinergic or glutamatergic inputs during cue presentation dampens the development of anticipatory approach responding to the food receptacle during the cue. Furthermore, we employed in vivo optetrode recordings to show that photoinhibition of PPTg cholinergic or glutamatergic inputs significantly decreases VTA non-dopamine (non-DA) neural activity. Consistently, photoinhibition of VTA non-DA neurons disrupts the development of cue-elicited anticipatory approach responding. Taken together, our study reveals a crucial regulatory mechanism by PPTg excitatory inputs onto VTA non-DA neurons during appetitive Pavlovian conditioning.
authors: Synaptic Plasticity Section, Intramural Research Program, National Institute on Drug Abuse, NIH, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA; Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei 10051, Taiwan.
authors: Hau-Jie
authors: HJ
authors: Yau
authors: Neurocircuitry of Motivation Section, Intramural Research Program, National Institute on Drug Abuse, NIH, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA.
authors: Dong V
authors: DV
authors: Wang
authors: Synaptic Plasticity Section, Intramural Research Program, National Institute on Drug Abuse, NIH, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA.
authors: Jen-Hui
authors: JH
authors: Tsou
authors: Institute of Public Health, National Yang-Ming University, Taipei 112, Taiwan.
authors: Yi-Fang
authors: YF
authors: Chuang
authors: Synaptic Plasticity Section, Intramural Research Program, National Institute on Drug Abuse, NIH, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA; Ionis Pharmaceuticals Inc., Carlsbad, CA 92010, USA.
authors: Billy T
authors: BT
authors: Chen
authors: Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering and Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors: Karl
authors: K
authors: Deisseroth
authors: Neurocircuitry of Motivation Section, Intramural Research Program, National Institute on Drug Abuse, NIH, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA.
authors: Satoshi
authors: S
authors: Ikemoto
authors: Synaptic Plasticity Section, Intramural Research Program, National Institute on Drug Abuse, NIH, U.S. Department of Health and Human Services, Baltimore, MD 21224, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: antonello.bonci@nih.gov.
authors: Antonello
authors: A
authors: Bonci
mesh_terms: D000818:Animals; D001066:Appetite / Q000502:physiology* / Q000528:radiation effects; D003214:Conditioning, Classical / Q000502:physiology* / Q000528:radiation effects; D003463:Cues; D059290:Dopaminergic Neurons / Q000502:physiology* / Q000528:radiation effects; D005971:Glutamates / Q000378:metabolism; D007858:Learning; D008027:Light; D008297:Male; D008810:Mice, Inbred C57BL; D045042:Pedunculopontine Tegmental Nucleus / Q000502:physiology* / Q000528:radiation effects; D012201:Reward; D017557:Ventral Tegmental Area / Q000502:physiology* / Q000528:radiation effects
chemical_list: D005971:Glutamates
keywords: PPTg; VTA; VTA non-DA neurons; appetitive Pavlovian conditioning; cholinergic input; glutamatergic input; pedunculopontine tegmental nucleus; ventral tegmental area