From valence encoding to motivated behavior: A focus on the nucleus accumbens circuitry

How do our brains determine whether something is good or bad? The brain's ability to evaluate stimuli as positive or negative – by attributing valence - is fundamental to survival and decision-making. Different brain regions have been associated with valence encoding, including the nucleus accumbens (NAc). The NAc is predominantly composed of GABAergic medium spiny neurons (MSNs), which segregate into two distinct populations based on their dopamine receptor expression: D1-receptor-expressing (D1-MSNs) and D2-receptor-expressing neurons (D2-MSNs). Classical models propose a binary functional role, where D1-MSNs exclusively mediated reward and positive valence, while D2-MSNs processed aversion and negative valence. However, we now recognize that NAc MSN subpopulations operate in a more complex manner than previously thought, often working cooperatively rather than antagonistically in valence-related behaviors. This review synthesizes our current knowledge of valence-encoding neurocircuitry, with emphasis on the NAc. We examine electrophysiological, calcium imaging, optogenetic, chemogenetic and pharmacological studies detailing the contribution of NAc medium spiny neurons for rewarding and aversive responses. Finally, we explore emerging technical innovations that promise to advance our understanding of how the mammalian brain encodes valence and translates it into behavior.