The nucleus accumbens (NAc) plays an important role in the acquisition and expression of many stimulus- reward associations, a process which can be co-opted by drugs of abuse. Information processing in the NAc is thought to be regulated by incoming glutamatergic signals from multiple areas, but the dynamic properties of these different signals are not well understood. This project will focus on the role of three prominent inputs arising from the medial prefrontal cortex, basolateral amygdala, and ventral hippocampus. Studies have begun to reveal the role of these pathways in mediating behavior guided by both natural rewards and drugs of abuse. However, it is still largely unknown to what extent the coordination of NAc neural dynamics with each of those inputs is modulated by experience, dopaminergic signaling, or reward type. The goal of this project is to address these issues using innovative approaches that combine large-scale neural recordings, optogenetics, and reward conditioning in mice.
The first aim i s to use large-scale neural recordings to determine whether synchrony between the NAc and the three designated inputs is differentially modified during associative reward learning. Additionally, this aim will determine the role of midbrain dopaminergic signaling in input selection, by using transient optogenetic suppression of dopamine neuron activity to modulate synchrony between the NAc and its inputs.
The second aim i s to combine neural recordings and transient optogenetic suppression of individual input signals to the NAc, to deconstruct the role of specific inputs in shaping neural coding and task performance at different stages of training. The goal in the third aim is to determine how, during periods of reward abstinence, neural synchrony between the NAc and its inputs is differentially modulated by cues previously associated with cocaine or food. Together, this study will greatly advance our understanding of how reward-related information processing in the nucleus accumbens is influenced by signals from three important and functionally diverse input sources.

Public Health Relevance

The ability to learn from rewards is a critical aspect of brain function, but the circuits that are involved in this process are also implicated in drug abuse. The nucleus accumbens is an important reward processing area that receives signals from a wide range of inputs. This project will investigate how inputs from three functionally diverse areas (medial prefrontal cortex, basolateral amygdala, and ventral hippocampus) differentially influence reward-related information processing in the nucleus accumbens during associative reward learning or abstinence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA042739-03
Application #
9720849
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Sorensen, Roger
Project Start
2017-08-01
Project End
2022-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Neurosciences
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Li, Bingzhao; Lee, Kwang; Masmanidis, Sotiris C et al. (2018) A nanofabricated optoelectronic probe for manipulating and recording neural dynamics. J Neural Eng 15:046008