Previous work has shown frequency-specific modulation of dorsal hippocampus (dHPC) neural activity during simple behavioral tasks, suggesting shifts in neural population activity during different task phases and animal behaviors. Relatively little is known about task-relevant orchestrated shifts in theta, beta, and gamma rhythms across multiple behavioral timescales during a complex task that requires repeatedly adapting behavioral strategies based on changing reward contingencies. To address this gap in knowledge, we used a spatial set-shifting task to determine whether dHPC plays a specific role in strategy switching. The task requires rats to use two spatial strategies on an elevated plus maze: 1) alternating between East and West reward locations or 2) always going to the same reward location (e.g., only East or only West). Across specific timescales (session based alignments, comparisons of trial types, within trial epochs), dHPC associates differentially with all three temporal categories. Across a session, we observe a decrease in theta and beta power before, and an increase in theta power after, the target strategy changes. Beta power is increased around the point at which rats learn the current rule. Comparing trial types, on trials before a rat has learned the correct strategy, beta power is increased. Within a single trial, after an incorrect (but not correct) choice, beta and gamma power increase while the rat returns to start a new trial. If gamma (but not beta) power was high during this return, the rat is more likely to make a correct choice on the next trial. On the other hand, low gamma power during the return is associated with incorrect trials. dHPC, therefore, appears to track task demands, with the strength of each rhythmic frequency differentially associating with specific behaviors across three distinct timescales.

Behavioral flexibility is the ability of an animal to adapt to environmental changes, crucial decision making and goal directed behaviors. Impaired behavioral flexibility has been linked to psychiatric disorders such as depression, anxiety, and substance use disorders. Emerging research suggests that psilocybin, a psychedelic drug that acts on serotonin receptors, may improve behavioral flexibility by promoting adaptability in responses to new information. Given the growing literature exploring the impact of psilocybin as a therapeutic treatment for psychiatric disorders, this study aims to explore the effects of psilocybin on the use of behavioral strategies on a complex spatial set-shifting task. Long-Evans rats were trained on an elevated plus maze with two start arms, north and south, and two reward arms, west and east. The task requires rats to alternate between two strategies: alternation and place. The alternation phase required rats to switch between reward arms (go West, then go East), and the place strategy required choosing the same arm (e.g. go West) continuously. Rats must determine the correct strategy and implement it; once 12 out of 15 trials are accurately completed, an uncued switch in the correct strategy will occur, requiring adaptation to a new strategy. Once animals were well-trained on the task, a single dose of psilocybin (1mg/kg) or saline was administered 10 minutes prior to a session and their behavior was analyzed. Metrics such as performance, and flexibility scores were assessed to determine the impact of psilocybin on behavior. Preliminary findings suggest psilocybin improves behavioral flexibility compared to the saline group, though overall performance remains relatively stable. These results provide insight into the potential of psilocybin as a therapeutic tool for conditions characterized by behavioral rigidity; even in wild-type animals, psilocybin improves flexibility, indicating the possibility for mitigating more severe impairments in flexibility seen in psychiatric disorders.