The role of rapid BLA glutamatergic signaling in reward-seeking decisions

University Of California Los Angeles, Los Angeles CA

Investigators

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Abstract

DESCRIPTION (provided by applicant): Drugs of abuse cause persistent changes in brain function, leading to long lasting changes in behavior. A common finding from studies of drug abuse is that drug exposure may result in disruption of the cognitive processes normally responsible for adaptive decision making, resulting in relapse to drug-seeking behavior and subsequent drug use. Accumulating evidence shows that these persistent changes in brain function are mediated by altered excitatory glutamatergic neurotransmission. Recently, it has become clear that excitatory glutamatergic neurotransmission is involved in normal reward-seeking actions. Several things, such as cues in the environment that trigger actions, can control reward-seeking actions. Importantly, reward-seeking decisions are also controlled by the anticipated value of an outcome, which enables us to choose a path leading to the most desirable outcome. A major gap in the literature remains in the neurochemical mechanisms and circuits underlying value-based decision-making under normal need-states and drug-induced disorder. The primary goal of this proposal incorporates sophisticated behavioral, pharmacological, and advance neurochemical monitoring approaches to examine how glutamatergic signaling relates to value-guided decisions. The first aim of this research proposal is to determine how rapid glutamate transients relate to discrete behaviors of reward seeking. Glutamate processes have been implicated in learning about reward values to guide decisions and very recently, rapid changes in glutamate concentrations have recently been shown to predict reward seeking generally. This raises the possibility that rapid changes in glutamate concentrations are involved in learning about reward values necessary for adaptive decision-making. The second aim will examine cortical inputs contributing to glutamatergic signals related to value-guided decision-making. The focus of the third aim is to examine how glutamatergic signals are altered by chronic opiate exposure. In all three aims, I will be using an innovative electroenzymatic method that allows for the temporally and spatially precise detection of rapid glutamate concentration changes. The experiments in this proposal will elucidate the role of glutamatergic signaling in value-guided reward seeking. This will not only significantly impact our basic understanding of decision-making processes, but more importantly, could also elucidate why addicts engage in maladaptive decisions and provide new strategies to prevent its occurrence.