Neurons of the Ventral Tegmental Area Encode Individual Differences in Motivational “Wanting” for Reward Cues

Abstract

It has been argued that the dopaminergic system is involved in the attribution of motivational value to reward predictive cues as well as prediction error. To evaluate, dopamine neurons were recorded from male rats performing a Pavlovian approach task containing cues that have both "predictive" and "incentive" properties. All animals learned the predictive nature of the cue (illuminated lever entry into cage), but some also found the cue to be attractive and were motivated toward it ("sign-trackers," STs). "Goal-trackers" (GTs) predominantly approached the location of reward receptacle. Rats were implanted with tetrodes for neural electrophysiological recordings in the ventral tegmental area. Cells were characterized by spike waveform shape and firing rate. Firing rates and magnitudes of responses in relation to Pavlovian behaviors, cue presentation, and reward delivery were assessed. We identified 103 dopamine and 141 nondopamine neurons. GTs and STs both showed responses to the initial lever presentation (CS1) and lever retraction (CS2). However, higher firing rates were sustained during the lever interaction period only in STs. Further, dopamine cells of STs showed a significantly higher proportion of cells responding to both CS1 and CS2. These are the first results to show that neurons from the VTA encode both predictive and incentive cues, support an important role for dopamine neurons in the attribution of incentive salience to reward-paired cues, and underscore the consequences of potential differences in motivational behavior between individuals.

Dopamine Circuit Mechanisms of Addiction-Like Behaviors

“…For example, humans with genetic polymorphisms that result in elevated DA system activity show greater reward cue-evoked striatal activity and craving that could denote a predisposition toward exaggerated drug use (Wittmann et al, 2013;Ray et al, 2014). Consistent with this, in animal models, variability in DA signaling and expression of striatal DA receptors is associated with higher drug cue responsivity and relapse (Flagel et al, 2007;Verheij and Cools, 2008;Piray et al, 2010;Saunders et al, 2013;Klanker et al, 2015;Ferguson et al, 2020). Furthermore, at certain stages of the estrus cycle, female rodents have larger NAc DA signals in response to cocaine and cocaine-associated cues, which is thought to underlie their generally higher propensity for addiction-like behaviors (Becker and Cha, 1989;Becker, 1999;Calipari et al, 2017;Johnson et al, 2019).…”

Distinct role of nucleus accumbens D2-MSN projections to ventral pallidum in different phases of motivated behavior

“…In addition, we showed that brief optical activation of D2-MSNs paired with a reward-predicting cue enhances motivation to obtain food rewards ( Soares-Cunha et al., 2016b , 2018 ). Part of this behavioral effect was triggered by a transient decrease in the activity of VP GABAergic neurons that resulted in the disinhibition of VTA dopaminergic activity ( Soares-Cunha et al., 2018 , 2020 ), which is known to increase motivational levels ( Ferguson et al., 2020 ; Ilango et al., 2014 ; Mohebi et al., 2019 ). However, others showed that chemogenetic inhibition of D2-MSNs during a progressive ratio task enhances motivation, without affecting sensitivity for reward devaluation ( Carvalho Poyraz et al., 2016 ), and causes animals to initiate more frequently behavior without goal-directed efficiency ( Gallo et al., 2018 ), an effect caused by disinhibition of VP GABAergic activity ( Gallo et al., 2018 ).…”

The Neurobiology of Behavior and Its Applicability for Animal Welfare: A Review

“…The seeking system consists mainly of dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain [ 23 ] and its projections to the nucleus accumbens (NAc) in the ventral striatum and prefrontal (PFC) and frontal (FC) cortices ( Figure 3 A). Following exposure to relevant stimuli dopamine (DA) is released to the synaptic cleft where it binds DA receptors [ 24 , 25 , 26 ]. One study in primates showed that DA release occurred following unexpected rewards (food), but also following exposure to conditioned stimulus (a light) and anticipated reward (food).…”