Here we seek to understand the neurochemical signals and neurosystems underlying reward-related decision- making. Considerable evidence suggests the decision between actions leading to different rewards relies heavily on the anticipated value of each action's outcome. In addition to this, reward-related decisions are also biased by reward-paired environmental cues, such that a cue predicting a specific reward will bias one towards the action that obtains that reward, even if other, potentially better, options ar available. Regarding the circuitry of reward-related decisions, numerous interconnected structures, including the basolateral amygdala, orbitofrontal cortex and insula are all implicated, but how or if they interact to control decisions remains unclear. Neurochemically, glutamate signaling and neuromodulatory opioid peptides are also implicated in aspects of reward seeking, but how these signals are related to discrete aspects of behavior has not been elucidated. Here we will use a novel glutamate biosensor technology, which allowed us, for the first time, to monitor transient extracellular glutamate concentration changes in the basolateral amygdala of freely-behaving rats, to clarify the role of rapid basolateral amygdala glutamate signaling in both reward learning and decision- making. Moreover, we will explore the basolateral amygdala-cortical circuitry that controls reward-seeking decisions. Given the limited number of signaling molecules in the brain, interactions between them must occur in order to account for the vast number of human behaviors. To this end, we will also explore the regulation of decision-related basolateral amygdala glutamate release by the neuromodulatory opioid peptide systems. The long-term goals of this research trajectory are to characterize the specific neurochemical signals that underlie discrete aspects of decision-making. Importantly, this research aims to identify brain regions and neurochemical systems that interact to underlie decisions driven by reward value as well as those that are biased by environmental cues. Each of these forms of decision-making can be disrupted in addiction to drugs, alcohol or even highly palatable foods. Therefore, information gleaned from this research trajectory will provide the basic science necessary for the development of new pharmacotherapies to combat these specific deviations in addiction and compulsive over-eating. Importantly, the proposed research makes use of a new tool, not yet applied to these questions, in order to provide new information regarding the role of brain glutamate signaling in reward-related behaviors.

Public Health Relevance

Addiction is often marked by maladaptive value-based decision-making and reward-related decisions excessively biased by drug-paired cues. This project assesses the neurosystems, focusing on basolateral amygdala glutamatergic signals, that underlie such value-based and cue-biased decision-making. Importantly, this research will inform the development of new pharmacotherapies that combat these specific deviations in addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA035443-05
Application #
9262905
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Su, Shelley
Project Start
2013-05-01
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2019-04-30
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Malvaez, Melissa; Greenfield, Venuz Y; Matheos, Dina P et al. (2018) Habits Are Negatively Regulated by Histone Deacetylase 3 in the Dorsal Striatum. Biol Psychiatry 84:383-392
Wassum, Kate M (2018) Clarifying punishment. Neuropsychopharmacology 43:1633-1634
Malvaez, Melissa; Wassum, Kate M (2018) Regulation of habit formation in the dorsal striatum. Curr Opin Behav Sci 20:67-74
Lichtenberg, Nina T; Wassum, Kate M (2017) Amygdala mu-opioid receptors mediate the motivating influence of cue-triggered reward expectations. Eur J Neurosci 45:381-387
Lichtenberg, Nina T; Pennington, Zachary T; Holley, Sandra M et al. (2017) Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations. J Neurosci 37:8374-8384
Wassum, Kate M; Greenfield, Venuz Y; Linker, Kay E et al. (2016) Inflated reward value in early opiate withdrawal. Addict Biol 21:221-33
Aitken, Tara J; Greenfield, Venuz Y; Wassum, Kate M (2016) Nucleus accumbens core dopamine signaling tracks the need-based motivational value of food-paired cues. J Neurochem 136:1026-36
Collins, Anne L; Aitken, Tara J; Greenfield, Venuz Y et al. (2016) Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation. Neuropsychopharmacology 41:2830-2838
Collins, Anne L; Greenfield, Venuz Y; Bye, Jeffrey K et al. (2016) Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation. Sci Rep 6:20231
Wassum, Kate M; Izquierdo, Alicia (2015) The basolateral amygdala in reward learning and addiction. Neurosci Biobehav Rev 57:271-83

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