2007 — 2009 |
Jones, Joshua L |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Amygdalar Regulation of Nucleus Accumbens Reward Signaling @ University of North Carolina Chapel Hill
[unreadable] DESCRIPTION (provided by applicant): Organisms direct actions towards specific goals and rewards, whether they are natural or drug rewards. It is essential for survival that actions result in successful pursuit of natural rewards, and often in the human condition, this pursuit can be usurped and directed towards unnatural rewards, such as drugs of abuse. Often these actions are guided by environmental cues and associations that may direct or influence the behavioral directions taken. These goal-directed actions, and the environmental associations relevant to them, likely involve the concerted activation of specific brain regions and neurotransmitter systems. The nucleus accumbens (NAc), often referred to as a limbic-motor interface, and its dopaminergic inputs are intimately involved in the modulation of food and drug reinforcement, specifically in the encoding of goal- directed action during self-administration. Furthermore, the amygdala, a related limbic structure, has been implicated in the formed association between environmental cues and predicted rewards. Together these structures likely form an integrated circuit regulating stimulus-reward associations. This proposal seeks to examine cellular and neurochemical activity in the NAc during a self-administration task, while simultaneously manipulating the amygdala and its NAc efferents. Multi-cellular electrophysiology and fast- scan cyclic voltammetry will be used to examine nucleus accumbens cell firing and subsecond dopamine release, respectively, during a self-administration paradigm. Functional manipulation of the amygdala will be accomplished using pharmacological microinjections. Taken together, the results of this study will provide insight into the functional circuitry involved in the neural encoding of goal-directed behaviors and the environmental cues associated with them. Relevance to Public Health: One of the most debilitating aspects of drug addiction is the susceptibility to relapse (resumption of drug taking after long periods of abstaining), often triggered by the environment or situation associated with previous drug taking. In the effort to understand addictive behaviors, we must first understand the underlying biological mechanisms of how things around us become associated with the rewards we take. This proposal seeks to describe the circuitry of these mechanisms, and in so doing provide key information for the development of pharmacological treatments for drug addiction in humans. [unreadable] [unreadable] [unreadable]
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1 |
2011 — 2013 |
Jones, Joshua L |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Dopamine Signaling of Expected Outcomes Within the Striatum @ University of Maryland Baltimore
DESCRIPTION (provided by applicant): Rewards are not procured and consumed in a vacuum. Rather, organisms learn to optimize behaviors through associations formed between relevant environmental stimuli and actions that consistently predict rewards. Numerous psychiatric conditions, including addiction, lead to aberrant decision-making in which people continue to respond to previously rewarded cues despite now adverse or undesirable consequences. As such, understanding the neural circuitry of such maladaptive learning processes is critical to developing successful therapeutic approaches. A diverse network of neural substrates, including regions of the ventral (VS) and dorsal striatum (DS) and their dopaminergic input from the midbrain, have been heavily implicated in reward learning. Here, we aim to test the hypothesis that cue-evoked dopamine signaling within the ventral and dorsal striatum has access to information about changes in the value of an expected outcome. Behaviorally, we can test this hypothesis by utilizing a reinforcer devaluation paradigm to establish what is known about the current value of a predicted outcome. Importantly, we know that conditioned responding in this behavioral paradigm is dependent on activity of the orbitofrontal cortex, and sensitive to cocaine induced dysfunction. Here, we will use fast-scan cyclic voltammetry and pharmacological manipulations (of the orbitofrontal cortex) in an outcome devaluation procedure, to provide novel characterization of striatal dopamine signaling. Furthermore, we will examine how prior cocaine experience alters striatal dopamine signaling within this task. Taken together, these studies will significantly advance our understanding of dopamine signaling of expected value, and more clearly define its role in reinforcement learning. PUBLIC HEALTH RELEVANCE: Numerous psychiatric conditions, including drug addiction, are associated with cognitive deficits that impair the ability to represent and use expected outcomes to guide appropriate responding, potentially reflecting modifications within learning circuits that mediate these behaviors. In an effort to understand these cognitive deficits, we must first understand the biological mechanisms that mediate them. This proposal seeks to provide a novel characterization of the role of dopamine in learning and processing of expected outcomes, particularly involving changes following chronic cocaine exposure, in an effort to provide key information for the development of therapeutic treatments for psychiatric conditions in humans.
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0.937 |