Riccardo Mozzachiodi - US grants

Abstract
Exposure to aversive stimuli drives an organism to budget its behaviors by augmenting certain responses and reducing/suppressing others. Characterizing how experience differentially regulates the activity of behaviorally-relevant neural circuits is paramount to understand the means by which external stimuli produces distinct behavioral modifications.
The long-term goal of this project is to analyze the effects of an aversive experience on distinct behaviors, using the mollusk Aplysia californica. This model system permits one to directly relate behavioral modifications to changes in the underlying neuronal circuits and, further, to modifications in identified neurons. When presented with repeated noxious stimuli, Aplysia exhibits a well-characterized long-term (> 24 h) learned enhancement of defensive responses (i.e., long-term sensitization, LTS) and a previously unexplored long-term suppression of a non-defensive behavior (i.e., feeding). In addition, aversive experience reduces the excitability of B51, a ?decision-making? neuron critical for the elicitation of feeding. The goals of this project are to: 1) analyze the neurophysiological mechanisms underlying the long-term suppression of feeding induced by LTS training at both the circuit and single-cell levels and 2) develop an in vitro preparation that co-expresses cellular correlates of both sensitization and suppression of feeding.
This project will be conducted at Texas A&M University ? Corpus Christi, which is a Hispanic-Serving Institution serving the population of South Texas. The proposed research activities will contribute to broadening participation of Hispanic and other underrepresented groups, by providing neuroscience training opportunities for the students of South Texas. The experiments will be conducted mainly by graduate students, under the supervision and mentorship of the PI. Undergraduate students will also engage in neurophysiology research by participating in all the aspects of the project.

DESCRIPTION (provided by applicant): The experience of an aversive event produces in animals and in humans profound and diffuse changes within the brain. For example, in the healthy brain, exposure to an aversive event requires balancing the expression of defensive and non-defensive behaviors. Deficits in the formation, maintenance and flexibility of this balance can lead to mental-health problems, such as anxiety disorders and post-traumatic stress disorder. Therefore, characterizing the mechanisms by which experience regulates the expression of multiple behaviors represents a critical step to understand medical conditions affecting millions of Americans. In the marine mollusk Aplysia californica, exposure to aversive stimuli induces the concurrent modulation of defensive and non-defensive behaviors. Specifically, aversive stimuli induce two opposite behavioral changes: a learned enhancement of defensive responses (i.e., sensitization) and a suppression of feeding behavior. Sensitization and suppression of feeding share analogous time courses that depend on the amount of aversive stimulation. Whereas the cellular and molecular mechanisms underlying sensitization in Aplysia have been extensively characterized, those underlying the suppression of feeding remain largely unknown. The PI's lab has recently begun to analyze the cellular and biochemical underpinning of the suppression of feeding induced by aversive stimuli. At the cellular level, the suppression of feeding is accompanied by a decreased excitability of a decision-making neuron (B51) critical for the expression of feeding. Recent evidence indicates that suppression of feeding and decreased B51 excitability are, at least in part, mediated by the cyclic GMP signaling cascade. In addition, serotonin, which mediates sensitization in Aplysia, does not alter either feeding or B51 excitability, suggesting that changes in the defensive and feeding neural circuits produced by aversive stimuli may be mediated by distinct and/or multiple neuromodulator(s). Using a combination of in vivo and in vitro procedures, this project will: 1) characterize the intracellular signals responsible for feeding suppression of and B51 decreased excitability by examining the role of the cGMP signaling cascade; 2) identify which neuromodulator mediates the suppression of feeding and decreased B51 excitability by investigating the contribution of a nitric oxide dependent pathway and 3) explore the relationship between sensitization and feeding suppression, by attempting to uncouple these two behavioral changes by manipulating the animal's motivational state and extending the exposure to aversive stimuli. The experiments outlined in this project propose a detailed analysis of the mechanisms responsible for the modulation of multiple behaviorally-relevant neural circuits by experience. This line of research in Aplysia will contribute to the understanding of how non-defensive neural circuits change their activity and their relations with defensive circuits in response to aversive stimuli in more complex animals, including humans.