There is a fundamental gap between human psychological experiences and how we study them in animal models. Humans typically learn and experience emotions within a variety of social contexts. By contrast, animal models are typically studied within an isolated environment. This discontinuity in social context imposes an obstacle to the development of treatments for psychological disorders. We propose a series of experiments that examine learning within the context of social interaction. The proposed experiments will allow us to develop and characterize new procedures for studying fear conditioning and extinction in the rodent laboratory, resulting in a novel conceptual framework for understanding the environmental, genetic, and molecular mechanisms that underlie learning and memory. To evaluate the interplay between learning and psychosocial experience, we need an environment sufficiently robust to impart translational relevance, yet simple enough to be accessible to multiple laboratories for routine assessments of genetically modified mice. Through a novel integration of readily available experimental tools, our model will focus on how different shared social experiences and non-social stimuli modulate the acquisition and extinction of fearful behaviors.
In Aim 1, we propose to determine how two critical features of social interaction, familiarity and social motivation, influence the capacity for vicarious fear learning. In the proposed experimental paradigm, a subject mouse observes an object mouse receive cued fear conditioning, repeated trials in which a tone is paired with a shock. Depending upon the strain of mice tested, C57BL/6J (B6), BALB/cJ (BALB), or FVB/NJ (FVB), the subject mouse then expresses a conditioned fear response to the tone. We ask whether the capacity of a subject mouse to learn from an object mouse is sensitive to its social motivation and its familiarity with the animal undergoing the tone-shock contingency.
In Aim 2, we ask how these same social variables, social motivation and familiarity, moderate the ability of a mouse to suppress a fearful memory; how social factors moderate fear extinction. We propose to examine juvenile mice of the B6, BALB, and FVB strains because they show robust fear conditioning yet differ in key social behaviors. B6 mice express greater levels of social interaction, social reward and vicarious fear learning relative to BALB mice. By comparing these three strains, we gain substantial insight to the role of social motivation in learning and extinction. We envision the proposed study will lead to a larger research program that reveals how social mechanisms enhance memory formation and extinction and that it will lead to novel models for a range of disorders that involve memory and social components, including PTSD, addiction, and autism.
Social experience is critically involved in the development, maintenance, and treatment of many psychiatric disorders. This project will employ a novel approach for incorporating social conditions into widely used mouse models of learned fear. By addressing the issue of social context in learning with a well-characterized model of mouse sociability, we will build a bridge between social and cognitive neuroscience that is essential for translation progress in this long overlooked aspect of human experience.
| Williams, Amy R; Lattal, K Matthew (2018) Rapid reacquisition of contextual fear following extinction in mice: effects of amount of extinction, acute ethanol withdrawal, and ethanol intoxication. Psychopharmacology (Berl) : |
| Hemstedt, Thekla J; Lattal, K Matthew; Wood, Marcelo A (2017) Reconsolidation and extinction: Using epigenetic signatures to challenge conventional wisdom. Neurobiol Learn Mem 142:55-65 |
