Charles L. Pickens - US grants

PROJECT SUMMARY Flexible decision-making, a form of cognitive/behavioral plasticity, is important for adapting to changing demands and circumstances in the world. The devaluation task is an animal model used to investigate the neuronal substrates of flexible decision-making. Laboratory models of decision-making using the devaluation task limit the response options available and the cues indicating the outcomes of these responses. However, the individual brain areas involved in devaluation are highly dependent on the model task used, and this simplification of the task can lead to versions of the devaluation task not requiring certain brain areas that are activated in human devaluation experiments and that are required for flexible human decision-making. The proposed research will validate that a task that is more similar to the human decision-making environment, with its multiple-response contingencies and cues that signal the contingencies, can be used to investigate the neural circuits of devaluation. One specific aim will investigate a devaluation task that more closely resembles human decision- making to ensure that it is sensitive to inactivation during learning of three key brain areas involved in flexible decision-making in humans, the basolateral amygdala (BLA), mediodorsal thalamus (MD), and orbitofrontal cortex (OFC). A second aim will then investigate whether interactions between these brain areas are necessary for learning the information necessary for the devaluation task. We will selectively inactivate connections between MD and the other two brain areas with microinjections of a chemogenetic virus (selectively activated by a normally inert ligand) into one brain area and microinjections of the ligand into a second brain area. The third aim will also determine whether these brains areas communicate with one another through direct projection by combining retrograde tracer injections into OFC with the neuronal activity marker Fos after a devaluation test. This will determine if the neurons in BLA and MD that project to OFC are the same neurons that are active during a devaluation test. The effects of disrupting BLA function on neuronal communication between MD and OFC will also be investigated. The results of these experiments will be potentially significant for understanding the brain circuitry that is responsible for adaptive and maladaptive plasticity that can lead to human decision-making function and dysfunction. Determining the exact nature of the neurobiological circuits for decision-making will promote the further development of targeted therapeutic techniques to mitigate decision-making impairments that could result from injuries, exposure to drugs of abuse or other toxins, genetic disorders, or other developmental problems. The project?s strong emphasis on examining the circuits-level plasticity that occurs during learning, and how alterations in this plasticity can have a detrimental effect on later goal-directed action, will also advance the C-NAP mission, enhancing the cross-cutting C-NAP research theme of the neurobiology of reward and decision.

PROJECT SUMMARY The current Behavioral Neuroscience (BN) core facility, housed within the Department of Psychological Sciences at Kansas State University (KSU), is the only dedicated BN core in Psychology in the State of Kansas. The BN core facility will be modernized and augmented through conducting alterations and renovations, and adding major equipment items to expand the capabilities of the facility. The BN core is a fully functional research core that was purpose-built in the early 1980s, and currently services 20-30 users including the BN PhD program. The core facility improvements will focus on the surgery, microscopy, wet laboratory, and cage wash facilities. The upgrades will expand the range of technologies available in the facility, allowing for the inclusion of cutting- edge techniques into current and future research programs. The core is directed by Dr. Stephen Kiefer, a nationally-known researcher in Behavioral Neuroscience in the area of taste-reactivity and alcohol abuse. Dr. Kirkpatrick (the COBRE PI/PD) will serve as associate director of the core to provide additional senior leadership. Additional training and mentoring will be supplied by the COBRE mentoring team, external advisory committee members, and members from the BN collaborative network at KSU. A veterinary technician will provide daily facility cleaning and maintenance, and will meet the animal care and husbandry needs of facility users. The BN core will directly support two of the primary projects (Cain and Pickens), the current community of users (including the PI/PD), potential pilot grant holders, and the additions of new faculty, post-doctoral fellow(s) and graduate students. The expansion of the core facilities will also support Cognitive and Neurobiological Approaches to Plasticity (C-NAP) center programs by providing an excellent training environment for the post-doctoral training program and contributing to the scientific exchange network (SEN) training. Most importantly the BN core upgrades will improve the research infrastructure for animal model research at KSU. Overall, the BN core facility will provide an important component to the attainment of the C-NAP overarching aims by contributing importantly to the success and growth of animal models of plasticity, a central component of C-NAP.