Wednesday, April 23, 2025
4/23/2025
Revealing activity signatures of early life adversity in the basolateral amygdala driving risky decision making - PROJECT SUMMARY Traumatic events experienced early in life can shift the behavioral repertoire in adolescence and adulthood, causing increases in risk seeking behaviors. These risky behavioral changes can lead to consequences such as motor vehicle accidents, increased sexual behaviors, and drug and alcohol abuse. The likelihood of making a risky decision is highest in adolescence, when unfortunately, the consequences may be the most severe and life altering. Understanding the ways in which early life adversity (ELA) increases adolescent propensity for risk taking is essential to preventing this maladaptive response, which can lead to harmful outcomes. ELA alters cellular function and activity in areas responsible for control of risky behaviors, including the basolateral amygdala (BLA), nucleus accumbens (NAc), and prefrontal cortex (PFC). The connectivity between these areas is responsible for assessing threat, responding to novel stimuli, and assessing valence, all of which are essential for safety related behaviors. The BLA is particularly poised to control risky behaviors and is also vulnerable to ELA related changes, including increases in neuronal excitability, making the BLA an incredibly valuable region to study when investigating ELA induced risk taking. Thus, examining activity changes to the BLA during ELA and manipulating ELA-impacted BLA ensemble activity during a risky decision-making task (RDT) will uncover a targetable neural mechanism underpinning adolescent maladaptive behavior. The RDT is a suitable task to assess risk taking because it measures an animal’s probability to choose a risky reward under variable probabilities of known risk, which is a shared core feature of risky decision making across species and therefore provides translational insight. In my previous work in the Brenhouse lab, I use a maternal separation (MS) model to assess adolescent changes in anxiety-like behaviors following chronic BLA inhibition. I found that rats exposed to MS exhibited decreased anxiety behaviors in adolescence as evidenced by increased exploratory behavior, which was contrary to my original hypothesis. This led me to design the current proposal, as I hypothesize that MS can drive increased risk taking in adolescence by recruiting BLA neuronal populations to be hyperexcitable. In Aim 1, I will test for ELA-driven changes to BLA cellular activity profiles by using RNAscope to examine increased immediate early gene expression in glutamatergic and GABAergic cells within the BLA following various time points of MS or control rearing. In Aim 2 I will tag cells with an activity dependent viral vector during MS, and then optogenetically excite or inhibit these cells during the RDT in order to test the ability of MS-affected cells to drive changes to risky behaviors. Ultimately the resulting discoveries from this project will contribute to the understanding of how ELA alters risk taking behaviors in adolescence and inform strategies to develop treatments for disordered behaviors involving increased risk seeking. The training I will receive through this F31 award will aid in my goals of becoming a well-rounded independent researcher focused on studying animal models of disease following ELA.
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