Scientific Understanding of Consciousness
Nucleus Accumbens Controls Risky Decision-Making
Nature 531, 642–646 (31 March 2016)
Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making
Kelly A. Zalocusky, et. al.
Bioengineering Department, Stanford University, Stanford, California 94305, USA
Neurosciences Program, Stanford University, Stanford, California 94305, USA
CNC Program, Stanford University, Stanford, California 94305, USA
Psychology Department, Stanford University, Stanford, California 94305, USA
Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA
A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making—either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making.
Previous work has implicated ventral tegmental area dopamine neurons, as well as their downstream targets (including NAc, prefrontal cortex, and orbitofrontal cortex (OFC)) in risk-preference. Ventral tegmental area stimulation, for example, has been shown to increase risk-seeking choices, and pharmacological manipulations have implicated dopamine release in NAc and prefrontal cortex in modulating risk-preference.
We devised a task in which rats repeatedly chose between a ‘safe’ lever, which yielded the same volume of sucrose on every trial, and a ‘risky’ lever, which yielded a small reward on 75% of trials and a large reward on 25% of trials. The expected value was constant across the two levers. Each day, each rat performed 50 forced choice trials, in which only one lever entered the operant chamber, followed by 200 free choice trials, in which both levers entered the chamber, allowing the rat to choose. The less favourable outcome of risky lever selection represented a loss relative to the expected value of each trial; we refer to this outcome as a loss. Each trial was initiated with a 1-s nosepoke hold just prior to lever press; we refer to this temporal window as the decision period.
In summary, we developed behavioural, genetic, imaging and optical stimulation methods for measuring and modulating neural dynamics underlying trait and trial-by-trial variation in risk preference. We observed neural correlates of risky choice in D2R+ NAc cells, and optogenetically demonstrated the causal role of neural activity in this genetically and spatially defined population of neurons in risky choice. Together, these findings suggest individual differences in risk preference can be explained at the behavioural level by divergent responses to loss, and at the neural level by NAc D2R+ cell responses to previous unfavourable outcomes.
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