Layered Reward Signalling Through Octopamine and Dopamine in Drosophila: A Dissertation

Evaluating our environment by deciding what is beneficial or harmful, pleasant or punishing is a part of our daily lives. Seeking pleasure and avoiding pain is a common trait all mobile organisms exhibit and understanding how rewarding stimuli are represented in the brain remains a major goal of neuroscience. Studying reward learning in the fruit fly, Drosophila melanogaster has enabled us to better understand the complex neural circuit mechanisms involved in reward processing in the brain. By conditioning flies with sugars of differing nutritional properties, we determined that flies trained with sweet but non-nutritive sugars formed robust short-term memory (STM), but not long-term memory (LTM). However, flies conditioned with a sweet and nutritious sugar or a sweet non-nutritious sugar supplemented with a tasteless nutritious compound, formed robust 24 hour LTM. These findings led us to propose a model of parallel reinforcement pathways for appetitive olfactory conditioning in the fly, in which both sweet taste and nutrient value contribute to appetitive long-term memory. We followed this line of research by examining the neural circuitry in the fly brain that represents these parallel reward pathways. We found that the biogenic amine octopamine (OA) only represents the reinforcing effects of sweet taste. Stimulation of OA neurons could replace sugar in olfactory conditioning to form appetitive STM. Surprisingly, implanting memory with OA was dependent on dopamine (DA) signaling, which although being long associated with reward in mammals, was previously linked with punishment in flies. We found that OA-reinforced memory functions through the α-adrenergic OAMB receptor in a novel subset of rewarding DA neurons that innervate the mushroom body (MB). The rewarding population of DA neurons is required for sweet and nutrient reinforced memory suggesting they may integrate both signals to drive appetitive LTM formation. In addition, OA implanted memory requires concurrent modulation of negatively reinforcing DA neurons through the β-adrenergic OCTβ2R receptor. These data provide a new layered reward model in Drosophila in which OA modulates distinct populations of both positive and negative coding DA neurons. Therefore, the reinforcement system in flies is more similar to that of mammals than previously thought

Winning the Battle, Losing the War?: Judicial Scrutiny of Prisoners\u27 Statutory Claims Under the Americans with Disabilities Act

When he was convicted in 1994 of drunken driving, escape, and resisting arrest, Ronald Yeskey was sentenced to serve 18 to 36 months in a Pennsylvania prison. In addition, the judge recommended that Yeskey be sent to a motivational boot camp operated by the state. Upon successful completion of the boot camp program, Yeskey\u27s sentence would then be reduced to six months. Although he eagerly wanted to participate, the prison refused him entrance into the boot camp program because of his history of hypertension, and also denied him admission into an alternative program for the disabled. As a result, he was incarcerated for two years and two months longer than he might have been had he successfully completed the boot camp. Yeskey filed suit in federal court, charging that prison authorities had violated his rights under the Americans with Disabilities Act (ADA) by discriminating against him due to his physical condition. On June 15, 1998, that suit reached the Supreme Court. In Pennsylvania Department of Corrections v. Yeskey the Court resolved a long-running circuit split in holding that Title II of the ADA applies to inmates in state prisons. The Court concluded that Ronald Yeskey\u27s claim under the Act should not have been barred due to his status as a prisoner. The Yeskey decision promises to have far-reaching legal consequences. It has prompted many commentators to predict a flood of lawsuits from disabled prisoners. The Court\u27s ruling was lauded by others as a victory for the disabled prison population, as it may provide a mechanism for inmates to improve correctional conditions regarding diverse issues, such as the physical protection of disabled inmates or the reform of prison healthcare systems. Yet for all of the fanfare it received, Yeskey failed to address an equally consequential issue that has the potential to blunt the force of the Supreme Court\u27s ruling significantly: the level of judicial scrutiny that prisoners\u27 ADA claims should receive