Exposure to aversive stimuli triggers an adaptive balance between defensive and appetitive behaviors, which, for survival, needs to be acquired rapidly, stored over time, and must be flexible to accommodate modifications in the organism?s internal and/or external state. A detailed characterization of the mechanisms underlying the formation, storage and flexibility of the balance is critical to understand how this fundamental process operates to help organisms survive in a changing environment. In the model organism Aplysia, exposure to aversive stimuli induces a balance that manifests as concurrent enhancement of defensive reflexes (an elementary form of learning known as sensitization) and suppression of the appetitive behavior of feeding. This balance is stored in short-term (minutes to hours) and long-term (days) timeframes depending on the amount of aversive exposure. The balance is sustained, at least in part, by changes at key sites within the corresponding neural circuits: decreased excitability of feeding decision-making neuron B51 co-expressed with increased excitability of the sensory neurons controlling defensive reflexes. The PI?s lab has begun to analyze the cellular and biochemical mechanism of the balance. Short-term sensitization and feeding suppression are mediated by distinct modulators, serotonin (5-HT) and nitric oxide (NO), respectively. Conversely, long-term sensitization and feeding suppression share the requirement of NO. Although sensitization and feeding suppression are concurrently induced following aversive experience, the long-term storage of sensitization following multiple days of repeated exposures to aversive stimuli has been found to outlast the suppression of feeding, suggesting the presence of constraints that may limit the maintenance of the balance over time. Using a combination of in vivo and in vitro procedures, this R15 AREA grant will: 1) determine whether common plasticity rules govern changes in feeding and defensive circuits; 2) further characterize the modulatory systems underlying the storage of the balance and 3) examine flexibility and constraints in the storage of the balance. The outcomes will contribute to the fundamental understanding of how the balance between defensive and appetitive behaviors in generated and stored in the normal nervous system. The acquired knowledge may ultimately provide important insights into those neurological disorders caused by deficits in the correct formation, storage and flexibility of this balance, thus aligning with the mission of the National Institute of Neurological Disorders & Stroke. The proposed experiments will be performed primarily by undergraduate students, under the supervision of the PI, research associate and/or a senior graduate student(s). This project represents a unique opportunity for Texas A&M University ? Corpus Christi, a Hispanic-Serving Institution, to increase its visibility in biomedical research, and for its undergraduate students to conduct research in the field of neuroscience, which is underrepresented at this institution.
A fundamental brain function necessary for survival is to balance the expression of defensive and non-defensive behaviors following an aversive experience. The overall goal of this proposal is to characterize the formation, storage and flexibility of this balance at the behavioral and neural-circuit levels. The acquired knowledge may ultimately provide important insights into those neurological disorders in which the correct balance between defensive and non-defensive behaviors is disrupted.
