Utilizing environmental information to predict future positive and negative outcomes is a behavioral adaptation that is essential for survival. While this process is required for the control of natural motivated behavioral responding to obtain rewards, the neural circuits that encode cue-reward associations are thought to be dysfunctional in neuropsychiatric disorders such as addiction. Therefore, it is essential that further research is conducted to delineate the neural mechanism that underlie responses to reward-predictive cues in an effort to uncover specific neural circuit elements that mediate this phenomena. Signaling by midbrain dopamine neurons is thought to play an important role in controlling the formation and expression of cue-induced reward seeking. In this proposal, we aim to study neural circuit elements within the ventral midbrain that may be important for activating or inhibiting dopaminergic function and therefore influence the acquisition and expression of cue-reward associations. To accomplish this, we will take a multifaceted approach. We will perform in vitro slice electrophysiological experiments to characterize the functional connectivity between specific excitatory inputs to dopaminergic and GABAergic neurons within the midbrain. In addition, we will use in vivo optogenetic stimulation/inhibition experiments to establish or refute causal relationships between genetically and anatomically defined neural circuit elements in the midbrain and the release of dopamine in the nucleus accumbens to reward-predictive cues. The information gained from these studies may greatly advance our understanding of the neural circuits that encode cue-reward associations.

Public Health Relevance

Psychiatric and neurological diseases and disorders have a tremendous impact on society. Despite improved diagnosis and treatment, further advancement is significantly hindered by a lack of understanding how alterations in neural circuit function leads to the development and expression of disease states. The research directions outlined in this proposal will characterize the function of key neural circuits that are involved in psychiatric disease such as substance abuse disorders. We aim to study these neural circuit elements in order to identify potentially novel therapeutic targets for the treatment neuropsychiatric disorders.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Pilotte, Nancy S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
Zip Code
Stuber, Garret D; Wise, Roy A (2016) Lateral hypothalamic circuits for feeding and reward. Nat Neurosci 19:198-205
Albaugh, Daniel L; Salzwedel, Andrew; Van Den Berge, Nathalie et al. (2016) Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens. Sci Rep 6:31613
Berrios, Janet; Stamatakis, Alice M; Kantak, Pranish A et al. (2016) Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimulation. Nat Commun 7:10702
Stamatakis, Alice M; Van Swieten, Maaike; Basiri, Marcus L et al. (2016) Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Regulate Feeding and Reward. J Neurosci 36:302-11
Decot, Heather K; Namboodiri, Vijay M K; Gao, Wei et al. (2016) Coordination of Brain-Wide Activity Dynamics by Dopaminergic Neurons. Neuropsychopharmacology :
Resendez, Shanna L; Jennings, Josh H; Ung, Randall L et al. (2016) Visualization of cortical, subcortical and deep brain neural circuit dynamics during naturalistic mammalian behavior with head-mounted microscopes and chronically implanted lenses. Nat Protoc 11:566-97
Jennings, Joshua H; Ung, Randall L; Resendez, Shanna L et al. (2015) Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell 160:516-27
McHenry, Jenna A; Rubinow, David R; Stuber, Garret D (2015) Maternally responsive neurons in the bed nucleus of the stria terminalis and medial preoptic area: Putative circuits for regulating anxiety and reward. Front Neuroendocrinol 38:65-72
Resendez, Shanna L; Stuber, Garret D (2015) In vivo calcium imaging to illuminate neurocircuit activity dynamics underlying naturalistic behavior. Neuropsychopharmacology 40:238-9
Stuber, Garret D; Stamatakis, Alice M; Kantak, Pranish A (2015) Considerations when using cre-driver rodent lines for studying ventral tegmental area circuitry. Neuron 85:439-45

Showing the most recent 10 out of 29 publications