Neuron-type-specific signals for reward and punishment in the ventral tegmental area

Abstract

Dopamine plays a key role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (i.e., reward prediction error, RPE)1-3, but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neurons based on responses to odours and outcomes: approximately half of the neurons (Type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with RPE coding. The other half of neurons showed persistent activity during the delay between odour and outcome, that was modulated positively (Type II, 31%) or negatively (Type III, 17%) by the value of outcomes. While the activity of Type I neurons was sensitive to actual outcomes (i.e., when the reward was delivered as expected vs. unexpectedly omitted), the activity of Types II and III neurons was determined predominantly by reward-predicting odours. We “tagged” dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 (ChR2) and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of Type I and all GABAergic neurons were of Type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate RPE.

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

“…Quantification revealed that 40.7% (1,415/3,481) of tyrosine hydroxylase (TH)-positive neurons were positive for ChR2-YFP in the VTA. The ability of ChR2 to excite VTA DA neurons in DAT-cre mice has been previously validated (31,32).…”

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

“…The mesocorticolimbic dopaminergic system, composed of dopaminergic neurons and their projections, has been proven to be involved in the reward‐motivated behaviors of individuals (Cohen, Haesler, Vong, Lowell, & Uchida, 2012; Ikemoto, 2007). The dopaminergic neurons are mainly located in the ventral tegmental area (VTA) (Beckstead, Domesick, & Nauta,1979) and project primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy).…”

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

“…The present data strengthen a dopamine-suppressive action of aversive stimuli that is consistent with investigations of discrete stimuli in awake and behaving subjects. These studies utilize electrophysiological and electrochemical recordings to demonstrate pauses in dopamine neuron firing (Cohen et al, 2012;Matsumoto and Hikosaka, 2009;Mirenowicz and Schultz, 1996) and dopamine release (Badrinarayan et al, 2012;Roitman et al, 2008;Wheeler et al, 2011) in the NAc following discrete aversive stimuli. Our work extends these findings to include a dopamine-suppressive action of an agent, LiCl, which produces a long-lasting aversive state Tomasiewicz et al, 2006).…”

“…Discrete aversive stimuli evoke pauses in the firing rate of a clear majority of dopamine neurons (Cohen et al, 2012;Matsumoto and Hikosaka, 2009;Mirenowicz and Schultz, 1996) and suppress phasic dopamine release in the NAc (Badrinarayan et al, 2012;Oleson et al, 2012;Roitman et al, 2008;Wheeler et al, 2011; but also see Anstrom et al, 2009;Brischoux et al, 2009;Budygin et al, 2012;Park et al, 2015 for reported increases in phasic dopamine activity to aversive stimuli under some conditions). However, while discrete stimuli are commonly used to study phasic dopamine responses, the time domain of aversive stimuli can range from discrete to prolonged.…”

“…Phasic increases in the firing of midbrain ventral tegmental (VTA) dopamine neurons and resulting phasic increases in extracellular nucleus accumbens (NAc) dopamine concentration occur both spontaneously and in response to either unconditioned primary rewards or conditioned predictors of reward (Cohen et al, 2012;Joshua et al, 2008;Matsumoto and Hikosaka, 2009;Owesson-White et al, 2012;Roitman et al, 2004;Schultz, 1998;Sombers et al, 2009;Zweifel et al, 2009). These phasic increases are both necessary and sufficient for positive reinforcement and associative learning (Steinberg et al, 2013;Tsai et al, 2009), supporting a mechanism by which rewarding stimuli reinforce approach behaviors necessary for survival (eg procuring food).…”