
David M. Lovinger PhD, Chief
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
5625 Fishers Lane, Room TS-13A:MSC 9411
Bethesda MD 20892-9412
telephone: 301.443.2445
fax: +1 301.480.0466
e-mail: lovingdav@mail.nih.gov
Mission Statement
Neurobiology of Action
We study the neurobiology of action in health and disease.
To study actions is to study the way we do things, which is different than studying how we remember stimuli, or facts and events. Some actions are innate or pre-wired (like swallowing, breathing, even grooming). Others are learned through trial and error throughout life. We currently focus on understanding the processes mediating the latter.
Our overall goal is to understand how changes in molecular networks in the brain modify neural circuits to produce experience-dependent changes in actions. In order to understand how actions are learned through trial and error, we subdivided our experiments in different components, or specific goals:
Action initiation: how do we initiate and generate diverse actions (trial),
Action improvement: how do we improve the accuracy and speed of actions (through trial and error), and.
Actions and outcomes: how do we learn that particular actions lead to particular outcomes (goal of the action) and how do we form habits.
Understanding how we automate actions and form habits will hopefully point us to the mechanisms underlying drug seeking in addiction.
A growing body of evidence supports an important role of the basal ganglia in action initiation and selection, in skill learning, and in learning goal-directed actions and habits. Therefore, we centered our efforts on investigating the cortico-basal ganglia mechanisms underlying these three processes using an across-level approach, from molecules to circuits.
We chose to implement this integrative approach in mice because they combine the power of genetics, a mammalian brain with canonical cortico-basal ganglia loops that can generate and propagate oscillatory activity, and the possibility of accurately quantifying simple behaviors like action initiation (with EMG recordings or using inertial sensors) and stereotypic skill learning, and more elaborate behaviors like goal-directed actions.
Our research program will hopefully shed light on the mechanisms underlying the diversity of actions we perform, the automatization of actions and the generalization rules or ways to do. Our research may also have important implications for understanding the relation between corticostriatal dysfunction and different neurodegenerative and psychiatric disorders.
SC Lin @ 2006
Current Members
Lakeasha Mingo; Administrative Lab Manager; lmingo@mail.nih.gov
Elizabeth Kirby; Secretary; kirbye@mail.nih.gov
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Rui M. Costa, DVM, PhD, Guest Researcher costarui@mail.nih.gov |
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Tina Gremel, PhD Post-doctoral fellow gremelc@mail.nih.gov
Current projects: Corticostriatal control of goal-directed and habitual behavior. |
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Guohong Cui, MD, PhD Post-doctoral fellow cuig@mail.nih.gov
Current projects: Dopamine and reinforcement learning, imaging gene expression in-vivo.
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Xin Jin, PhD Post-doctoral fellow jinx@mail.nih.gov
Current projects: Reward and action selection.
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Amber Luo, MD Research Associate gluo@mail.nih.gov
Current projects: Notch signaling in the adult brain, inducible cre lines, restricted channelrhodopsin lines. |
Section Alumni
Monica Hilario, currently at University of Pennsylvania
Terrell Holloway, currently at Mount Sinai University
Christine White, currently at University of Michigan
Elissa Gerfen, currently at Vanderbilt University
Emily Clouse, currently at University of Maryland
Shweta Prasad-Mulcare, currently at NIH/NIBIB
Michael Pham, currently at Georgetown University
Eduardo Dias Ferreira, currently at Champalimaud Neuroscience Program, Instituto Gulbenkian de Ciencia, Portugal
John Burkhardt, currently at Champalimaud Neuroscience Program, Instituto Gulbenkian de Ciencia, Portugal
Selected Publications
Yin, H.H., Prasad-Mulcare, S., Hilario, M.R.F., Clouse, E., Davis, M. I., Lovinger, D.M.., Costa, R.M. (2008). Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill. Nature Neuroscience, In Press.
Hilario, M.R.F and Costa, R.M. (2008). High on Habits. Frontiers in Neuroscience, 2,2:208-21,
http://frontiersin.org/neuroscience/paper/10.3389/neuro.01/030.2008/
Cui, Y., Costa R. M., Murphy G. G., Elgersma, Y., Zhu, Y., Gutmann, D.H., Parada, L.F., Mody, I., Silva A. J. (2008). Neurofibromin regulation of Ras/ERK signaling modulates GABA release and learning. Cell, 31;135(3):549-60.
Hilario, M., Clouse, E., Yin, H.H., Costa, R.M. (2007). Endocannabinoid signaling is critical for habit formation. Frontiers in Integrative Neuroscience. 1:6, http://www.frontiersin.org/integrativeneuroscience/paper/10.3389/neuro.07/006.2007/
Costa, R.M., Lin, S.C., Sotnikova, T.D., Cyr, M., Gainetdinov, R.R., Caron, M.G., Nicolelis M.A.L. (2006). Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction. Neuron, 52(2):359-69.
Costa, R.M., Drew, C. and Silva, A.J. (2005). To Remember or Notch to Remember. Trends in Neurosciences, 28, 429-35.
Costa, R.M.*, Cohen, D.*, Nicolelis M.A.L. (2004). Differential corticostriatal plasticity during fast and slow motor skill learning in mice. Current Biology, 14(13):1124-34.
Costa R.M., Honjo T., and Silva A.J. (2003). Learning and memory deficits in Notch mutant mice. Current Biology, 13 (15): 1348-54. Costa, R.M. and Silva, A.J. (2003). Mouse models of Neurofibromatosis type I: Bridging the GAP. Trends in Molecular Medicine, 9, 19-23.
Costa, R.M., Federov, N.B., Kogan, J.H., Murphy, G.G., Stern, J., Ohno, M., Kucherlapati, R., Jacks, T. and Silva, A.J. (2002). Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature, 415 (6871):526-30.
Costa, R.M.*, Yang, T.*, Huynh, D.P., Pulst S.M., Viskochil, D.H., Silva, A.J. and Brannan, C.I. (2001). Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of the Neurofibromatosis type I gene. Nature Genetics, 27, 399-405.
Complete list of publications