The basal ganglia-habenula circuitry in reward processing the overall goal of this project is to investigate the basic brain mechanisms underlying reward processing. Recent studies demonstrate that the lateral habenula (LHb) provides valence signals to the midbrain dopamine areas. However, in part owing to the challenges in monitoring and manipulating activities in the LHb circuitry, the roles of this circuiry in more complex behaviors still remain elusive. In particular, how LHb neurons acquire the valence signals, and whether and how these signals are used to guide behavior, are questions that remain unresolved. Bridging these gaps is of great clinical significance, because LHb dysfunction is implicated in the pathogenesis of depression, a major psychiatric disorder in which deficit in reward processing is the hallmark. In the proposed study, we plan to approach these questions by investigating how functionally distinct groups of neurons in the basal ganglia-lateral habenula circuitry coordinate and participate in reward processing, thereby influencing behavior. For this purpose we have devised an integrated strategy that combines molecular genetic tools together with electrophysiological, imaging, optogenetic, chemogenetic, and behavioral techniques. Findings from this research program will provide novel insight into the synaptic, cellular, and circuit mechanisms by which the basal ganglia-lateral habenula circuitry contributes to reward-related processes.

Public Health Relevance

The neural mechanisms of reward processing remain unclear. In the proposed research program, we will determine the synaptic, cellular, and circuit mechanisms by which neurons in the basal ganglia-lateral habenula circuitry participate in reward-related processes. Findings from this project will have important clinical implications, as impairments in reward processing are core features of depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH108924-01
Application #
9019304
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Rossi, Andrew
Project Start
2015-09-28
Project End
2020-06-30
Budget Start
2015-09-28
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
$734,118
Indirect Cost
$351,765
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
Schiff, Hillary C; Bouhuis, Anna Lien; Yu, Kai et al. (2018) An Insula-Central Amygdala Circuit for Guiding Tastant-Reinforced Choice Behavior. J Neurosci 38:1418-1429
Yu, Kai; Ahrens, Sandra; Zhang, Xian et al. (2017) The central amygdala controls learning in the lateral amygdala. Nat Neurosci 20:1680-1685
Stephenson-Jones, Marcus; Yu, Kai; Ahrens, Sandra et al. (2016) A basal ganglia circuit for evaluating action outcomes. Nature 539:289-293
Baker, Phillip M; Jhou, Thomas; Li, Bo et al. (2016) The Lateral Habenula Circuitry: Reward Processing and Cognitive Control. J Neurosci 36:11482-11488