Mentor: Chandrashekhar Borkar, Ph.D.

Psychedelic compounds such as psilocybin are able to modulate brain activity mostly through serotonergic systems. Specifically, 5-HT2A receptors can lead to wide changes in neural signaling and plasticity. These compounds are able to create rapid changes in neuronal activation patterns and gene expression, especially in the cortical and limbic regions of the brain. Evidence continues to show that psychedelics produce changes in activity-dependent transcription, which makes them important tools to study neural plasticity mechanisms (Davoudian, 2023). One of the best ways to capture these rapid changes in the brain is through the study of Immediate Early Genes (IEGs). IEGs, such as c-Fos, are extensively used markers for neuronal activation. c-Fos is quickly expressed in response to pharmacological stimulation and usually shows activity-dependent transcriptional changes in neurons (Davoudian, 2023). In relation to this, psilocybin has been shown to increase c-Fos activation across multiple brain regions, which indicates the activation of cells (Funk, 2024). Immunohistochemistry (IHC) and immunofluorescence techniques make it possible to spatially visualize and quantify c-Fos-positive cells at high resolution, making it incredibly valuable to scientists. The brain regions that show off the most c-Fos are the prefrontal cortex (PFC), amygdala, and the Bed Nucleus of the Stria Terminalis (BNST). The PFC is crucial to processing higher-order integration and demonstrates a strong activation in c-Fos when exposed to psilocybin or psilocin. Similarly, the amygdala is involved in the regulation of emotion and stress, while the BNST is part of the extended amygdala and mostly involved in constant neural activation states (Funk, 2024). After exposure to psychedelics, c-Fos is expressed in great amounts, specifically in the central amygdala and in the BNST it shows that c-Fos is involved in larger limbic circuit modulation. Although psilocybin, a psychedelic that increases neural plasticity and c-Fos expression, is a very common psychedelic used to measure c-Fos expression, there are other psychedelics that cover the same area as well (Davoudian, 2023). Norbaeocystin also has significant effects on IEG expression and cellular activation, although little research has been conducted with it.

We hypothesized that the mice injected with Norbaeocystin would show more aggression related control compared to the mice injected with saline. This would be shown through the increased activation of c-Fos in the regions of the amygdala.

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