Neural and Cognitive Mechanisms Underlying Perseverance and Their Disruption After Juvenile Social Play Deprivation

About This Grant

PROJECT SUMMARY / ABSTRACT Early life adversity (ELA) is associated with a greater risk for later life substance use disorder and cognitive deficits. In contrast, positive social relationships can preclude the enduring effects of ELA. Isolation rearing in rodent models causes social deficits in adulthood, but the impact on executive functioning more generally and whether these effects are driven by the stress of isolation or the absence of social experiences in particular is unclear. Juvenile social play is uniquely poised to play a crucial role in neurocognitive development as it is, curiously, present only during the fleeting peri-adolescent window. This window of playfulness mirrors a period of tremendous synaptic refinement in cortical areas like the anterior cingulate cortex (ACC), a region that plays a vital role in adaptively guiding behavior in response to errors and emotional state. Is play simply correlated with adult decision-making, or could it actively shape development of the underlying neural mechanisms? Intriguingly, we have recently found via exploratory factor analysis that components of juvenile sociality are differentially related to adult cognition, informing our overall hypothesis that temporary social play deprivation during a critical period of development induces lasting differences to decision-making and risk for addiction in a rodent model. Aim 1 first characterizes a novel rodent task to assess the balance between drive and inhibition in the face of setbacks, providing training opportunities in task design and hardware construction. We will record from single neurons in ACC as rats perform this “Multi-Step Perseverance Task” (MSPT) to identify how the firing of ensembles contributes to the psychological constructs that mediate how effort, perseverance and resilience influence our drive towards a goal that requires multiple steps to achieve and often results in set-backs along the way. Aim 2 tests the hypothesis that temporary play deprivation at the juvenile age induces lasting impacts on multiple aspects of neurocognition and oxycodone self-administration. Animals will be specifically deprived of juvenile social play behavior by separation with a transparent, perforated barrier that still allows for limited, non-physical social interaction. We will assess their adult performance on our novel MSPT in combination with two standard, well-characterized rodent tasks—reward-guided decision-making and incubation of oxycodone craving—to together identify which facets of adult cognition are impacted by the absence of juvenile play. We predict that social play deprived rats, compared to pair-housed controls, will show less flexible decision-making and increased vulnerability to oxycodone relapse. By running all three tasks in the same animals, we can glean unique insight into the specific cognitive domains that are functionally altered by social play deprivation, enhanced by our use of sophisticated neurocomputational approaches. I will receive training from a diverse team of advisors that will support my short-term development towards my long-term goal of leading a laboratory focused on understanding the neurocircuit underpinnings of adaptable decision-making and how they are influenced by adverse experiences during critical periods of development.