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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA032750-03S1
Application #
8803135
Study Section
Program Officer
Pilotte, Nancy S
Project Start
2014-01-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2015-12-31
Support Year
3
Fiscal Year
2014
Total Cost
$98,607
Indirect Cost
$33,734
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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
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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

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