Member, Neuroscience GPB Home Area
Our lab is interested in how the brain learns to construct associative models of our environment. These models comprise events we’ve learnt to associate in the past and how all these events might be related. Building these models allows us to use our knowledge to flexibly change how we decide to respond (or learn) in the future. For example, when searching for coffee in an unfamiliar city, you might walk down the street in search of the particular signage associated with your favorite coffee store back home. The one which has the particular beans you prefer and know how to make your particular style of coffee. But failing this, you might default onto other predictors of good coffee. Instead, you might search for coffee shops with a queue out the front, an aroma indicating the presence of good espresso, or fancy artwork on top of lattes. This simple example illustrates the flexibility of decision making; we often integrate many aspects of our experience within our current context to influence our decision making.
Our lab studies the contribution of three regions of the brain to the different aspects of the decision-making process. In particular, how the midbrain dopamine system interacts with the lateral hypothalamus and prefrontal cortex to contribute to learnt representations of our experience. To investigate this, we use sophisticated behavioral designs in combination with optogenetics and fiber photometry in transgenic rodent models.
The eventual aim of this research is to understand how these processes go awry in psychopathology. For example, an inability to ignore irrelevant information in the environment is thought to contribute to the positive symptoms of schizophrenia, which typically include delusions and hallucinations. In the lab, we are trying to ask what neural circuits are disrupted in this disorder- contributing to these specific impairments in cognition, and eventually the symptoms- with the intention of providing pre-clinical work that informs the development of new treatments.
Find out more about our lab here: https://sharpelab.psych.ucla.edu/
A selected list of publications:
- Millard Samuel J, Bearden Carrie E, Karlsgodt Katherine H, Sharpe Melissa J The prediction-error hypothesis of schizophrenia: new data point to circuit-specific changes in dopamine activity Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022; 47(3): 628-640.
- DiFazio Lauren E, Fanselow Michael, Sharpe Melissa J The effect of stress and reward on encoding future fear memories Behavioural brain research, 2022; 417(3): 113587.
- Sharpe Melissa J, Batchelor Hannah M, Mueller Lauren E, Gardner Matthew P H, Schoenbaum Geoffrey Past experience shapes the neural circuits recruited for future learning Nature neuroscience, 2021; 24(3): 391-400.
- Seitz Benjamin M, Blaisdell Aaron P, Sharpe Melissa J Higher-Order Conditioning and Dopamine: Charting a Path Forward Frontiers in behavioral neuroscience, 2021; 15(3): 745388.
- Mueller Lauren E, Sharpe Melissa J, Stalnaker Thomas A, Wikenheiser Andrew M, Schoenbaum Geoffrey Prior Cocaine Use Alters the Normal Evolution of Information Coding in Striatal Ensembles during Value-Guided Decision-Making The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021; 41(2): 342-353.
- Hart Evan E, Sharpe Melissa J, Gardner Matthew Ph, Schoenbaum Geoffrey Responding to preconditioned cues is devaluation sensitive and requires orbitofrontal cortex during cue-cue learning eLife, 2020; 9(2): 342-353.
- Maes Etienne J P, Sharpe Melissa J, Usypchuk Alexandra A, Lozzi Megan, Chang Chun Yun, Gardner Matthew P H, Schoenbaum Geoffrey, Iordanova Mihaela D Causal evidence supporting the proposal that dopamine transients function as temporal difference prediction errors Nature neuroscience, 2020; .
- Sharpe Melissa J, Batchelor Hannah M, Mueller Lauren E, Yun Chang Chun, Maes Etienne J P, Niv Yael, Schoenbaum Geoffrey Dopamine transients do not act as model-free prediction errors during associative learning Nature communications, 2020; 11(1): 106.
- Sharpe Melissa J, Stalnaker Thomas, Schuck Nicolas W, Killcross Simon, Schoenbaum Geoffrey, Niv Yael An Integrated Model of Action Selection: Distinct Modes of Cortical Control of Striatal Decision Making Annual review of psychology, 2019; 70(1): 53-76.
- Sharpe Melissa J, Killcross Simon Modulation of attention and action in the medial prefrontal cortex of rats Psychological review, 2018; 125(5): 822-843.
- Sharpe Melissa J What a relief! A role for dopamine in positive (but not negative) valence Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018; 43(8): 1-2.
- Langdon Angela J, Sharpe Melissa J, Schoenbaum Geoffrey, Niv Yael Model-based predictions for dopamine Current opinion in neurobiology, 2018; 49(8): 1-7.
- Sharpe Melissa J, Schoenbaum Geoffrey Evaluation of the hypothesis that phasic dopamine constitutes a cached-value signal Neurobiology of learning and memory, 2017; 49(8): 1-7.
- Sharpe Melissa J, Batchelor Hannah M, Schoenbaum Geoffrey Preconditioned cues have no value eLife, 2017; 6(8): 1-7.
- Sharpe Melissa J, Marchant Nathan J, Whitaker Leslie R, Richie Christopher T, Zhang Yajun J, Campbell Erin J, Koivula Pyry P, Necarsulmer Julie C, Mejias-Aponte Carlos, Morales Marisela, Pickel James, Smith Jeffrey C, Niv Yael, Shaham Yavin, Harvey Brandon K, Schoenbaum Geoffrey Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning Current biology : CB, 2017; 27(14): 2089-2100.e5.
- Sharpe Melissa J, Chang Chun Yun, Liu Melissa A, Batchelor Hannah M, Mueller Lauren E, Jones Joshua L, Niv Yael, Schoenbaum Geoffrey Dopamine transients are sufficient and necessary for acquisition of model-based associations Nature neuroscience, 2017; 20(5): 735-742.
- Nasser Helen M, Calu Donna J, Schoenbaum Geoffrey, Sharpe Melissa J The Dopamine Prediction Error: Contributions to Associative Models of Reward Learning Frontiers in psychology, 2017; 8(5): 244.
- Sharpe Melissa J, Schoenbaum Geoffrey Back to basics: Making predictions in the orbitofrontal-amygdala circuit Neurobiology of learning and memory, 2016; 131(5): 201-6.
- Sharpe M J, Clemens K J, Morris M J, Westbrook R F Daily Exposure to Sucrose Impairs Subsequent Learning About Food Cues: A Role for Alterations in Ghrelin Signaling and Dopamine D2 Receptors Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016; 41(5): 1357-65.
- Sharpe Melissa J, Wikenheiser Andrew M, Niv Yael, Schoenbaum Geoffrey The State of the Orbitofrontal Cortex Neuron, 2015; 88(6): 1075-1077.
- Sharpe Melissa J, Killcross Simon The prelimbic cortex directs attention toward predictive cues during fear learning Learning & memory (Cold Spring Harbor, N.Y.), 2015; 22(6): 289-93.
- Sharpe Melissa, Killcross Simon The prelimbic cortex uses contextual cues to modulate responding towards predictive stimuli during fear renewal Neurobiology of learning and memory, 2015; 118(6): 20-9.
- Sharpe Melissa J, Killcross Simon The prelimbic cortex contributes to the down-regulation of attention toward redundant cues Cerebral cortex (New York, N.Y. : 1991), 2014; 24(4): 1066-74.
- Sharpe Melissa J, Killcross Simon The prelimbic cortex uses higher-order cues to modulate both the acquisition and expression of conditioned fear Frontiers in systems neuroscience, 2014; 8(6): 235.
- Sharpe Melissa J, Fardell Joanna E, Vardy Janette, Johnston Ian N The chemotherapy agent oxaliplatin impairs the renewal of fear to an extinguished conditioned stimulus in rats Behavioural brain research, 2012; 227(1): 295-9.