How the Brain Turns Down Fear to Turn Up Connection
Why do some neural signals increase our willingness to engage socially while others reinforce fear and avoidance? This project explores how a specific receptor, sphingosine-1-phosphate receptor 3 (S1PR3), may regulate the balance between social engagement and emotional inhibition by modulating communication between key brain regions involved in stress and behavior.
The research was presented at the Graduate Poster Exhibition during the 2025 SPARK (Showcase of Projects, Art, Research, and Knowledge), which highlights graduate research across disciplines. Developed within the Master of Science program in Biology at Rutgers University–Camden, this project was completed by Sai Anusha Jonnalagadda. The abstract below introduces her investigation into how S1PR3 signaling shapes neural circuits associated with sociability.
Abstract
Sphingosine-1-phosphate receptor 3 (S1PR3) plays a pivotal role in regulating social behavior by modulating neuronal activity in circuits involved in emotional regulation, notably the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Recent evidence suggests that S1PR3 activation enhances sociability by increasing neuronal activity in the infralimbic cortex (IL), which in turn suppresses BLA function. However, the molecular and cellular mechanisms underlying this interaction remain unclear. While S1PR3 activation excites both glutamatergic and GABAergic neurons, its ability to inhibit BLA activity presents a complex challenge for understanding how these divergent effects contribute to sociability. This research aims to explore how S1PR3 activation regulates neuronal signaling in the IL–BLA circuit and to elucidate the molecular and cellular processes involved.
To address this, key neuronal activity markers, including c-Fos, GAD, and NeuN, were quantified in the PFC, central amygdala (CeA), and BLA. These markers provide insight into neuronal activation and inhibition, helping to clarify the impact of S1PR3 modulation in these regions. A comparative analysis of treatment effects was conducted by examining expression levels in mice treated with CYM5541, an S1PR3 agonist, CAY10444, an S1PR3 antagonist, and vehicle-treated controls. This approach allowed assessment of the differential effects of S1PR3 activation and inhibition on neuronal activity in the PFC, CeA, and BLA.
Methods included systemic injections of CYM5541 and CAY10444 to modulate S1PR3, followed by social interaction and tail suspension tests to evaluate sociability and stress-related behaviors. Immunohistochemistry was used to detect specific neuronal markers in brain tissue, and confocal imaging provided high-resolution three-dimensional visualization of neuronal activity and receptor localization. Images were quantified using ImageJ and organized for analysis.
The implications of this research extend beyond basic neuroscience. Dysregulation in circuits involving the PFC and BLA is associated with neuropsychiatric conditions such as anxiety and depression. By clarifying how S1PR3 modulates activity within these pathways, this study contributes to identifying potential therapeutic targets for restoring balance in stress-related circuits and improving sociability.
Graduate Poster Exhibition at SPARK!
The Graduate Poster Exhibition celebrates the research and creative work of the graduate community, showcasing everything from prose and code to original research and artistic expression. As part of SPARK! (Showcase of Projects, Art, Research, and Knowledge), a reimagining of Research Week, the exhibition highlights the depth, range, and impact of graduate scholarship and invites the campus community to engage with ideas taking shape across disciplines.
Join a Legacy of Excellence in Biological Research
The Master of Science in Biology program at Rutgers University–Camden offers an immersive experience in diverse biological fields, including cell and molecular biology, neuroscience, physiology, and ecology. With a 50-year legacy, the program emphasizes research, analytical, and communication skills, preparing graduates for Ph.D. programs or careers in academic research and teaching. Students benefit from state-of-the-art facilities in the Science and Joint Health Science buildings and engage with internationally recognized faculty whose research spans RNA evolution, mitochondrial energetics, bacterial shape dynamics, and more.
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