My 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.
My 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.
Sharpe, M. J., Chang, C. Y., Liu, M. A., Batchelor, H. M., Mueller, L. E., Jones, J. L., Niv, Y. & Schoenbaum, G. (2017). Dopamine transients are sufficient and necessary for acquisition of model-based associations. Nature neuroscience, 20(5), 735.
Sharpe, M. J., Marchant, N. J., Whitaker, L. R., Richie, C. T., Zhang, Y. J., Campbell, E. J., Koivula, P.P., Necarsulmer, J.C., Mejias-Aponte, C., Marisela M., Pickel, J., Smith, J.C., Niv, Y., Shaham, Y., Harvey, B., & Schoenbaum, G. (2017). Lateral hypothalamic GABAergic neurons encode reward predictions that are relayed to the ventral tegmental area to regulate learning. Current Biology, 27(14), 2089-2100.
Nasser, H. M., Calu, D. J., Schoenbaum, G., & Sharpe, M. J.(2017). The dopamine prediction error: contributions to associative models of reward learning. Frontiers in psychology, 8, 244.
Sharpe, M. J., Wikenheiser, A. M., Niv, Y., & Schoenbaum, G. (2015). The state of the orbitofrontal cortex. Neuron, 88(6), 1075-1077.
Sharpe, M. J., & Killcross, S. (2015). The prelimbic cortex directs attention toward predictive cues during fear learning. Learning & Memory, 22(6), 289-293.
Sharpe, M. J., & Killcross, S. (2012). The prelimbic cortex contributes to the down-regulation of attention toward redundant cues. Cerebral cortex, 24(4), 1066-1074.