Hyper-sensitivity to light and sound 1-2 weeks post-concussion is a common symptom, and can persist in about 20% of patients up to months past injury. This is called Post-Concussion Syndrome (PCS); common symptoms of PCS include decreased cognitive function. Understanding these deficits can contribute to developing targeted interventions for cognitive dysfunction related to sensory sensitivity following brain injuries. We aimed to explore and determine the chronic effects of sensory dysregulation using a mouse model following repeat concussion injury on the Pairwise Visual Discrimination (PD), Reversal, and ReReversal task. We employed an innovative use of Touchscreen Operant Chambers to score behavioral outcomes, a method that has not been established in traumatic brain injury research. We developed a Standard Operating Procedure based on optimizations of experimental variables. We originally hypothesized that mice injured with the Repeated Closed Head Injury model (rCHI) would result in lower accuracy, increased time to complete trials, and greater latency for correct trial completion with audio distractors. However, the data showed no major significant differences between the groups with these variables, and thus necessitates a reevaluation of the original hypothesis. A novel trial-by-trial data analysis approach is in progress. Compared with previous behavioral assays previously performed, the rCHI mice are expected to show reduced discrimination accuracy and slower response times in the presence of a distractor.

Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation that elicits neural activity in a target region. rTMS over the prefrontal cortex (PFC) is effective for the treatment of major depressive disorder (MDD). However, the neural mechanisms underlying its therapeutic effects are poorly understood. To address this gap, our lab developed and validated a system to deliver clinical rTMS protocols in awake mice. Using an accelerated intermittent theta burst stimulation paradigm (aiTBS) we delivered rTMS to dorsomedial PFC (dmPFC) in mice exposed to 2 weeks of chronic corticosterone (CORT), a validated stress protocol. One day of aiTBS reversed behavioral deficits in several depression-related assays, but the microcircuit mechanisms underlying these changes are unclear. This project focused on three classes of inhibitory interneurons in PFC: parvalbumin (PV), somatostatin (SST) and vasoactive intestinal polypeptide (VIP). Fiber photometry recordings from each cell type showed that aiTBS differentially modulates activity from these interneurons in several depression-related behavioral assays. We studied these aiTBS-induced changes using platform mediated avoidance, an assay that presents stressed mice with a dynamic approach-avoidance conflict. We found that inhibiting SST cells during aiTBS blocks its antidepressant behavioral effects, suggesting that aiTBS drives prefrontal inhibitory plasticity to produce its therapeutic effects. These findings will help rationally optimize aiTBS in clinical settings.

Pain is the main indication for medical cannabis use, but prior research suggests cannabis may increase pain sensitivity during abstinence due to metabolite levels. We investigated the association between frequency of cannabis use, acute pain sensitivity, and circulating cannabinoid levels during periods of abstinence between participants who use cannabis more frequently (≥5 days of use/week, n=18) and less frequently (≤4 days of use/week, n=20). 38 healthy adults (20F, 18M) completed a Cold Pressor Test, and time to report pain (pain threshold) and time of hand withdrawal (pain tolerance) were recorded. Subjective pain ratings were measured with the Short-Form McGill Pain Questionnaire and the ‘Painfulness’ and ‘Bothersomeness’ scales. Blood was used to analyze cannabinoids: THC, 11-OH-THC, 11-COOH-THC, CBD, anandamide, 2-AG, OEA, and PEA. Pain threshold, tolerance, and subjective pain ratings did not differ between groups. THC, 11-OH-THC, and 11-COOH-THC levels were higher in individuals who use more frequently. Only THC (p = 0.02) and 11-OH-THC (p < 0.001) levels were positively related to subjective pain ratings. Cannabis use frequency wasn’t associated with acute pain sensitivity, but higher THC and 11-OH-THC levels in frequent users were linked to greater subjective pain. This contributes to the ongoing discussion when considering clinical use and study of cannabinoids as analgesic therapies, but more research is needed to explore different contexts.

Psychostimulant experience has been shown to produce aberrant activation patterns in brain regions that support learning about rewards and decision making, likely contributing to subsequent dysregulated use. There is growing evidence suggesting that subregions of the prefrontal cortex, such as orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), as well as dopaminergic midbrain regions, such as ventral tegmental area (VTA), may undergo changes in activity following drug experience. We examined how prior methamphetamine experience alters the expression of immediate early gene c-Fos using immunohistochemical techniques. Long-Evans rats (n=16, 8 female) gained a history of intermittent intravenous methamphetamine self-administration experience (n=8) or were drug-naïve (n=8) prior to euthanasia and brain collection. Forty micron-thick sections from each region were stained for c-Fos with cell counting conducted on the pixel ratios of c-Fos-to-DAPI (neuron) expression of the regions of interest using ImageJ, conducted by an observer blind to condition. Our preliminary results revealed a trend for an increase in VTA, but not OFC or ACC, c-Fos expression in the animals with methamphetamine experience compared to saline controls. This suggests there is differential timing and/or sensitivity to methamphetamine experience in reward vs. executive function areas, respectively. Ongoing experiments are aimed at characterizing the behavioral correlates of these changes.

This study investigates the developmental dynamics of neuronal lineages in the Drosophila embryonic brain using high-resolution electron microscopy (EM) datasets. By reconstructing and analyzing interactions between DALcm1/2 lineages and mushroom body neurons, it explores the hypothesis that specific recognition processes guide these lineages toward forming precise synaptic connections. The project employs advanced computational tools for 3D reconstruction to trace developmental trajectories and analyze growth cone interactions. Insights gained from this research will contribute to understanding how neurons establish functional circuits, with implications for developmental neurobiology, circuit formation, and behavioral neuroscience. These findings may also inform studies on neurodevelopmental disorders and provide a framework for exploring similar processes in other model organisms and humans (Spindler & Hartenstein, 2010).