Pontomesencephalic Tegmental Afferents to VTA Non-dopamine Neurons Are Necessary for Appetitive Pavlovian Learning

• Published in: Cell reports (Cambridge) Vol. 16; no. 10; pp. 2699 - 2710
• Main Authors: Yau, Hau-Jie, Wang, Dong V., Tsou, Jen-Hui, Chuang, Yi-Fang, Chen, Billy T., Deisseroth, Karl, Ikemoto, Satoshi, Bonci, Antonello
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.09.2016; Elsevier
• Subjects: Animals; Appetite - physiology; Appetite - radiation effects; appetitive Pavlovian conditioning; cholinergic input; Conditioning, Classical - physiology; Conditioning, Classical - radiation effects; Cues; Dopaminergic Neurons - physiology; Dopaminergic Neurons - radiation effects; glutamatergic input; Glutamates - metabolism; Learning; Light; Male; Mice, Inbred C57BL; pedunculopontine tegmental nucleus; Pedunculopontine Tegmental Nucleus - physiology; Pedunculopontine Tegmental Nucleus - radiation effects; PPTg; Reward; ventral tegmental area; Ventral Tegmental Area - physiology; Ventral Tegmental Area - radiation effects; VTA; VTA non-DA neurons; VTA; appetitive Pavlovian conditioning; ventral tegmental area; pedunculopontine tegmental nucleus; VTA non-DA neurons; PPTg; glutamatergic input; cholinergic input
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.08.007

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. [Display omitted] •We study how VTA afferent inputs modulate appetitive Pavlovian conditioning•PPTg-to-VTA excitatory inputs are required for proper cue-reward association•PPTg-to-VTA excitatory inputs support non-DA neural activity in vivo•VTA non-DA neural activity is necessary for appetitive Pavlovian conditioning VTA non-DA neurons are not solely interneurons. Yau et al. uncover regulation of VTA non-DA neurons by PPTg excitatory inputs during acquisition of Pavlovian cue-reward association, providing a DA-independent perspective on the study of appetitive Pavlovian conditioning.