The rostromedial tegmental (RMTg) "brake" on dopamine and behavior: A decade of progress but also much unfinished work. (15th October 2021) - Jhou, Thomas C.
Abstract: Between 2005 and 2009, several research groups identified a strikingly dense inhibitory input to midbrain dopamine neurons arising from a previously uncharted region posterior to the ventral tegmental area (VTA). This region is now denoted as either the rostromedial tegmental nucleus (RMTg) or the "tail of the VTA" (tVTA), and is recognized to express distinct genetic markers, encode negative "prediction errors" (inverse to dopamine neurons), and play critical roles in behavioral inhibition and punishment learning. RMTg neurons are also influenced by many categories of abused drugs, and may drive some aversive responses to such drugs, particularly cocaine and alcohol. However, despite much progress, many important questions remain about RMTg molecular/genetic properties, diversity of projection targets, and applications to addiction, depression, and other neuropsychiatric disorders. This article is part of the special Issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'. Highlights: The RMTg provides major GABAergic inputs to midbrain dopamine neurons. Many RMTg neurons are selectively activated by aversive stimuli and their predictors. RMTg inactivation profoundly impairs punishment but not reward or extinction learning. RMTg neurons contribute to aversion during withdrawal from abused drugs. A minority of RMTg neurons project to non-dopamine targets of unknown function.