Melissa Judith Sharpe

Princeton University | PU · Princeton NeuroScience Institute

Maladaptive decision-making is a hallmark of substance use disorders, though how drugs of abuse alter neural representations supporting adaptive behavior remains poorly understood. Past studies show the orbitofrontal (OFC) and prelimbic (PL) cortices are important for decision making, tracking both task-relevant and latent information. However, pre...

Studies investigating the neural mechanisms by which associations between cues and predicted outcomes control behavior often use associative learning frameworks to understand the neural control of behavior. These frameworks do not always account for the full range of effects that novelty can have on behavior and future associative learning. Here, i...

Experimental research controls for past experience, yet prior experience influences how we learn. Here, we tested whether we could recruit a neural population that usually encodes rewards to encode aversive events. Specifically, we found that GABAergic neurons in the lateral hypothalamus (LH) were not involved in learning about fear in naïve rats....

Substance use disorders (SUDs) are characterized by maladaptive behavior. The ability to properly adjust behavior according to changes in environmental contingencies necessitates the interlacing of existing memories with updated information. This can be achieved by assigning learning in different contexts to compartmentalized "states." Though not o...

The orbitofrontal cortex (OFC) is necessary for inferring value in tests of model-based reasoning, including in sensory preconditioning. This involvement could be accounted for by representation of value or by representation of broader associative structure. We recently reported neural correlates of such broader associative structure in OFC during...

The orbitofrontal cortex (OFC) is necessary for inferring value in tests of model-based reasoning, including in sensory preconditioning. This involvement could be accounted for by representation of value or by representation of broader associative structure. We recently reported neural correlates of such broader associative structure in OFC during...

The orbitofrontal cortex (OFC) is necessary for inferring value in tests of model-based reasoning, including in sensory preconditioning. This involvement could be accounted for by representation of value or by representation of broader associative structure. We recently reported neural correlates of such broader associative structure in OFC during...

Reward-evoked dopamine transients are well established as prediction errors. However, the central tenet of temporal difference accounts-that similar transients evoked by reward predictive cues also function as errors-remains untested. In the present communication we addressed this by showing that optogenetically shunting dopamine activity at the st...

Dopamine neurons are proposed to signal the reward prediction error in model-free reinforcement learning algorithms. This term represents the unpredicted or ‘excess’ value of the rewarding event, value that is then added to the intrinsic value of any antecedent cues, contexts or events. To support this proposal, proponents cite evidence that artifi...

Dopamine neurons fire transiently in response to unexpected rewards. These neural correlates are proposed to signal the reward prediction error described in model-free reinforcement learning algorithms. This error term represents the unpredicted or excess value of the rewarding event. In model-free reinforcement learning, this value is then stored...

Reward-evoked dopamine is well-established as a prediction error. However the central tenet of temporal difference accounts - that similar transients evoked by reward-predictive cues also function as errors - remains untested. To address this, we used two phenomena, second-order conditioning and blocking, in order to examine the role of dopamine in...

Making decisions in environments with few choice options is easy. We select the action that results in the most valued outcome. Making decisions in more complex environments, where the same action can produce different outcomes in different conditions, is much harder. In such circumstances, we propose that accurate action selection relies on top-do...

In the version of this article initially published, the laser activation at the start of cue X in experiment 1 was described in the first paragraph of the Results and in the third paragraph of the Experiment 1 section of the Methods as lasting 2 s; in fact, it lasted only 1 s. The error has been corrected in the HTML and PDF versions of the article...

Theories of functioning in the medial prefrontal cortex are distinct across appetitively and aversively motivated procedures. In the appetitive domain, it is argued that the medial prefrontal cortex is important for producing adaptive behavior when circumstances change. This view advocates a role for this region in using higher-order information to...

We have long known that dopamine encodes the predictive relationship between cues and rewards. But what about relief learning? In this issue of Neuropsychopharmacology, Meyer et al. show that the same circuits encoding rewarding events also encode relief from aversive events. And this appears to be in a manner distinct from encoding of the aversive...

The phasic dopamine error signal is currently argued to be synonymous with the prediction error in Sutton and Barto's (1987) model-free reinforcement learning algorithm (Schultz, Dayan, & Montague, 1997). This theory argues that phasic dopamine reflects a cached-value signal that endows reward-predictive cues with the scalar value inherent in rewar...

Phasic dopamine responses are thought to encode a prediction-error signal consistent with model-free reinforcement learning theories. However, a number of recent findings highlight the influence of model-based computations on dopamine responses, and suggest that dopamine prediction errors reflect more dimensions of an expected outcome than scalar r...

Sensory preconditioning has been used to implicate midbrain dopamine in model-based learning, contradicting the view that dopamine transients reflect model-free value. However, it has been suggested that model-free value might accrue directly to the preconditioned cue through mediated learning. Here, building on previous work (Sadacca et al., 2016)...

Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neurons in the control of the core motivation to feed, and their act...

Associative learning is driven by prediction errors. Dopamine transients correlate with these errors, which current interpretations limit to endowing cues with a scalar quantity reflecting the value of future rewards. We tested whether dopamine might act more broadly to support learning of an associative model of the environment. Using sensory prec...

Phasic activity of midbrain dopamine neurons is currently thought to encapsulate the prediction-error signal described in Sutton and Barto’s (1981) model-free reinforcement learning algorithm. This phasic signal is thought to contain information about the quantitative value of reward, which transfers to the reward-predictive cue after learning. Thi...

State representation is fundamental to behavior. However, identifying the true state of the world is challenging when explicit cues are ambiguous. Here, Bradfield and colleagues show that the medial OFC is critical for using associative information to discriminate ambiguous states. State representation is fundamental to behavior. However, identifyi...

The prevalence of hedonic foods and associated advertising slogans has contributed to the rise of the obesity epidemic in the modern world. Research has shown that intake of these foods disrupt dopaminergic systems. It may be that a disruption of these circuits produces aberrant learning about food-cue relationships. We found that rodents given 28...

The prelimbic cortex is argued to promote conditioned fear expression, at odds with appetitive research implicating this region in attentional processing. Consistent with an attentional account, we report that the effect of prelimbic lesions on fear expression depends on the degree of competition between contextual and discrete cues. Further, when...

The prelimbic (PL) cortex allows rodents to adapt their responding under changing experimental circumstances. In line with this, the PL cortex has been implicated in strategy set shifting, attentional set shifting, the resolution of response conflict, and the modulation of attention towards predictive stimuli. One interpretation of this research is...

Previous research suggests disruption of activity in the prelimbic (PL) cortex produces deficits in tasks requiring preferential attention toward cues that are good predictors of an event. By manipulating cue predictive power, we clarify this role using Pavlovian conditioning. Experiment 1a showed pretraining excitotoxic lesions of the PL cortex di...

Recent evidence has shown that diverse chemotherapy agents can induce cognitive impairments and neurotoxic damage to the central nervous system. Oxaliplatin (OXP), a platinum compound, has been linked with acute and chronic peripheral neuropathies. This study explored the cognitive impacts of OXP in the rat with a fear conditioning procedure. 10 da...