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

Hau-Jie Yau,Dong V Wang,Jen-Hui Tsou,Yi-Fang Chuang,Billy T Chen,Karl Deisseroth,Satoshi Ikemoto,Antonello Bonci

doi:10.1016/j.celrep.2016.08.007

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 invivo 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-elicitedanticipatory approach responding. Taken together, our study reveals a crucial regulatory mechanism by PPTg excitatory inputs onto VTA non-DA neurons during appetitive Pavlovian conditioning.

Highlights

The dopamine (DA) neurons in the ventral tegmental area (VTA) play a key role in appetitive reward associative learning (Fields et al, 2007; Steinberg et al, 2013; Wise, 2004)
The Development of Anticipatory Approach Responding during Pavlovian Conditioning We used an appetitive Pavlovian conditioning paradigm to study the functional contribution of pedunculopontine tegmental nucleus (PPTg)-to-VTA innervations
Photoinhibition of VTA Non-DA Neural Activity during Pavlovian Conditioning On the basis of these results, we propose that VTA non-DA neurons, which are subjected to the regulation by PPTg excitatory inputs, are necessary to develop conditioned responding during Pavlovian conditioning

Summary

Introduction

The dopamine (DA) neurons in the ventral tegmental area (VTA) play a key role in appetitive reward associative learning (Fields et al, 2007; Steinberg et al, 2013; Wise, 2004). During appetitive Pavlovian learning, midbrain DA neurons exhibit phasic burst firing activity to unconditioned appetitive stimuli (Ljungberg et al, 1991). In order to evolve the capability to drive DA neurons burst firing to the conditioned stimuli, the afferent inputs must have the ability to recruit midbrain VTA circuits, as unconditioned appetitive rewards do (Wise, 2004; Zellner and Ranaldi, 2010).

Results

Discussion

Conclusion