Chronic pain affects 20.9% of U.S. adults, and up to 25% develop opioid use disorder (OUD) (Goldberg & McGee, 2011). Although these conditions exacerbate one another, the neural mechanisms by which chronic pain increases relapse vulnerability remain unclear. Kappa opioid receptors (KORs) regulate nociceptive and stress-related processes. While systemic KOR activation produces analgesia, it also promotes stress-induced drug seeking. The central amygdala (CeA) integrates affective and pain signals and is required for stress-induced opioid relapse (Taylor et al., 2015). However, the role of CeA KORs under chronic pain conditions is unknown. To test whether right CeA KOR signaling mediates pain-related reinstatement, (KORflox/flox) mice received unilateral Cre infusions into the right CeA. Following chronic constriction injury (CCI) or sham surgery, mice underwent oxycodone conditioned place preference, extinction, and stress-induced reinstatement. Preliminary data suggest that CeA KOR deletion reduces reinstatement selectively in CCI mice, implicating right CeA KOR signaling in pain-enhanced relapse vulnerability.

Social behavior is shaped by chemical signals in the brain that help animals respond to their social world. One important signal is oxytocin, called the “love hormone” in humans because of its role in bonding, trust, and social connection. Differences in oxytocin signaling have also been linked to social patterns seen in autism, making it a key target for understanding how the brain regulates social behavior. In fish, a closely related molecule called isotocin plays a similar role. Some fish species, like the African Cichlid, live in dynamic hierarchies, where males can quickly rise from subordinate to dominant status, suggesting that brain chemistry helps drive these rapid changes. In this project, I asked whether isotocin is necessary for this kind of social “rise.” I predicted that fish lacking isotocin would be more likely to display aggression, and less likely to exhibit affiliative behaviors. To test this, I conducted mirror assays comparing fish with normal isotocin levels, reduced levels, and no functional isotocin. This was a pilot study, the results showed that fish with normal isotocin tend to display more social and affiliative behaviors than those without it. These findings suggest that isotocin plays an important role in activating social behavior in response to opportunity. More broadly, this work helps uncover the neural mechanisms behind social behavior and could contribute to better understanding, and eventually treating, social differences in humans.

The study’s goal is to understand how arousal, motivation, attention, and other external factors, including sleep and discomfort, are related to each other. In this study, participants completed weekly sessions, in which data on their performance on continuous performance and spatial memory tasks, along with electroencephalogram (EEG) recordings, were collected. On the day before the session, participants completed questionnaires that asked them about their state for the past week. On the day of the session, participants completed both a pre-session questionnaire and post-session questionnaire, which asked them about their immediate state. We found that motivation and attention were positively correlated with each other and negatively correlated with discomfort. The stress portion of arousal was negatively correlated with attention and motivation, whereas the non-stress portion of arousal was positively correlated with attention and motivation. These relationships were inconsistent across time frames(past week, pre-session, and post-session), and there was little internal correlation within the same measure across these different time frames. We also found variability in the relationships between the measures across individuals, which could help explain differences across individuals in neural markers, such as alpha power. An increased understanding of how motivation, attention, and arousal interact with each other and other environmental factors can be used to improve learning and engagement in school settings.

The Forkhead box protein 1 is a transcription factor, which is encoded by the Foxp1 gene. Mutations in Foxp1 lead to the development of FOXP1 syndrome with symptoms of autism spectrum disorder and motor dysfunction. FOXP1 is strongly expressed in different brain regions, including striatum, a key region involved in regulating motor skills and cognition. Striatum is primarily composed of two types of spiny projection neurons (SPNs) that are inhibitory in nature, and are named as D1 and D2 SPNs, based on the expression of Dopamine receptor 1 and 2 respectively. Foxp1 plays an important role in the development of both D1 and D2 SPNs. Embryonic loss of Foxp1 in D2 SPNs, leads to a significant reduction in the number of D2 SPNs. However the reason, mechanism, and what happens to the D2 SPNs is unknown. We hypothesize that some of the cells that are supposed to make D2 SPNs, change their fate into D1 SPNs in the absence of Foxp1. Using transgenic mice models, we will induce embryonic deletion of Foxp1 in D2 SPNs along with the YFP expression in the Drd2-cre expressing cells and tdTomato expression in D1 cells. We will collect these mice from both control and knockout groups at postnatal timepoints – P1, P9 and P18 and perform immunochemistry to analyze how the proportion of D1 SPNs and D2 SPNs change with Foxp1 deletion in developing striatum. The results from this research will be important for understanding the mechanism of the Foxp1 dependent regulation of D2 SPN development and to develop therapeutics for Foxp1 syndrome.

Down syndrome (DS), or Trisomy 21, is the most common genetic disorder causing intellectual disability. DS is characterized by learning and memory deficits and is linked to structural and functional abnormalities in the cortex (Cx). Studies have shown that DS brains exhibit an altered population of cortical GABAergic interneurons, suggesting altered neurogenesis and interneuron migration. Critical to functional Cx circuit formation and maintenance is the excitation–inhibition balance, regulated by GABAergic interneurons. Most inhibitory interneurons originate in the transient ganglionic eminence (GE) and migrate to the Cx. To characterize GABAergic interneuron development and migration to DS-relevant brain regions, we developed pilot region-specific organoids modeling the GE and Cx from control and DS hiPSC lines. To validate these pilots as human-relevant in vitro model, we performed immunohistochemistry for key developmental markers (PAX6, TBR2, BCL11B in Cx; NKX2.1, OLIG2, DLX1 in GE) and performed a qualitative evaluation of the pilot organoids. This work aims to identify the pathways underlying network dysfunction in DS, potentially informing therapeutic targets.