Reappraising striatal D1- and D2-neurons in reward and aversion

The striatum has been involved in complex behaviors such as motor control, learning, decision-making, reward and aversion. The striatum is mainly composed of medium spiny neurons (MSNs), typically divided into those expressing dopamine receptor D1, forming the so-called direct pathway, and those expressing D2 receptor (indirect pathway). For decades it has been proposed that these two populations exhibit opposing control over motor output, and recently, the same dichotomy has been proposed for valenced behaviors. Whereas D1-MSNs mediate reinforcement and reward, D2-MSNs have been associated with punishment and aversion. In this review we will discuss pharmacological, genetic and optogenetic studies that indicate that there is still controversy to what concerns the role of striatal D1- and D2-MSNs in this type of behaviors, highlighting the need to reconsider the early view that they mediate solely opposing aspects of valenced behaviour.CS-C and BC are recipients of Fundação para a Ciência e Tecnologia (FCT) fellowships (SFRH/BD/51992/2012; SFRH/BD/98675/2013). AJR is a FCT investigator (IF/00883/2013). Authors are funded by the Portuguese North Regional Operational Program (ON.2-O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER); and by the Projeto Estratégico − LA 26-2013–2014 (PEst-C/SAU/LA0026/2013).