Absence epilepsy is characterized by spike-and-wave discharges (SWD) in electroencephalographic (EEG) signals that correspond to cognitive and behavioral arrest in patients. Many studies have identified various physiological effects of absence epilepsy on human development, and pharmaceutical intervention has significantly improved the treatment of absence seizures. However, despite these advances there remains little understanding of mood and behavioral comorbidities commonly present in pediatric and adult patients with childhood-onset absence epilepsy. The Ank3 gene provides a unique opportunity to study these comorbidities, as it has been linked to mood disorders in human genetics studies and more recently to absence epilepsy in rodents. Thus, this study aims to identify unique event-related behavioral correlates in EEG signals of Ank3-knockout (KO) mice. Here, we take advantage of two supervised learning algorithms to identify SWD events from EEG recordings and to track the animals’ movements from the video recordings. The kinematic information produced from the movement tracking was then used to estimate behavioral states (e.g., sleeping and walking) via a personally developed algorithm that was cross validated by a subset of videos manually scored by an observer. Power of EEG signals during these behavioral states was estimated for signal frequencies between 1 and 50 Hz using a Morlet wavelet transform. Preliminary results suggest that KO mice exhibited increased slow gamma (~30-40 Hz) power during sleep and walking compared to wildtype controls. Preliminary results also suggest that these increases in slow gamma correlated with Ank3 gene dosage and seizure phenotype severity.

Post-traumatic stress disorder (PTSD) is one of the most prevalent co-occurring psychiatric pathologies among individuals with alcohol use disorder (AUD). Although comorbidity worsens the symptoms and prognosis following treatment of both disorders, no approved compound has demonstrated efficacy to treat AUD comorbid with PTSD. GABAergic neurosteroids are altered by chronic alcohol and play a role in the stress and arousal systems degraded in PTSD. Particularly, dampened plasma levels of allopregnanolone are found in individuals with alcohol dependence or undergoing alcohol withdrawal and individuals with PTSD. Our goal was to establish an animal model to explore the role that neurosteroid levels have in predicting drinking or stress reactivity in individuals exposed to social defeat. Male and female CFW mice were trained to aggress C57BL/6J intruders. Intruder mice received ten social defeat experiences with sex-matched aggressors. Blood samples were taken following the first defeat. Following chronic social defeat, mice were given limited access to alcohol (20%, v/v) 3 hours a day for 14 days to assess changes in the escalation of binge drinking for intruder mice and non-stressed controls. After a withdrawal period, tissue was harvested to assess neuronal response to stress or acute alcohol, using c-Fos immunoreactivity. Behaviors and images were coded by experimenters blinded to treatment groups. Future work will determine if these mice show variability in the effect that chronic stress has on binge drinking behavior and whether this variability may be predicted by changes in circulating neurosteroid levels in both males and females experiencing chronic stress.

Interruptions and distractions occur every day, and at times can be an inconvenience on one’s ability to perform simple daily tasks. To investigate the influence distractions have on attention and performance, this study will utilize eye tracking to conduct an examination of auditory distractions during two different workload conditions. Evidence from Kanaan & Moachdieh (2021) suggest that interruptions lead to slower and more limited search of visual information directly after the interruption in a high-workload condition, resulting in lower mean saccade amplitude and higher mean fixation duration. While the interruptions in Kanaan & Moachdieh (2021) study were relevant to the task, our study will focus on irrelevant auditory distractions that occur during the task. Participants primary task will be to monitor a computer screen and detect subtle changes in shapes on the screen. Changes will be noted for the objects they are able to detect by pressing a button on a gamepad. There will be a high-workload condition (7-9 shapes) and a low-workload condition (3-5 shapes), as well as two distraction conditions comprised of trials with irrelevant auditory distractions and trials without auditory distraction. Eye movements will be examined across conditions. We hypothesize that the results will align with Kanaan & Moachdieh (2021), with a higher mean fixation duration and a lower mean saccade amplitude after an auditory distraction in the high-workload condition, even though the auditory information is completely task irrelevant in our experiment.

The brains of patients with Alzheimer’s disease (AD), Parkinson’s Disease (PD), and related neurodegenerative diseases (NDD) often contain high levels of neurofibrillary tangles consisting of misfolded tau protein. Although these neurofibrillary tangles were previously believed to be the cause of neuronal dysfunction, recent work from our group instead suggests a truncated tau protein to be the main tau product involved in cognitive decline in NDD. This truncated tau species is present in higher levels in the brains of individuals with NDD and mice with cognitive impairment. The mechanism by which truncated tau is produced was previously unknown. Caspase-2 is a cellular protein involved in NMDAR mediated long-term depression (LTD). This work provides preliminary evidence that caspase-2 cleavage of tau underlies synaptic weakening in NDD. A mouse model was created with the aspartate at the cleavage site in tau changed to glutamate, rendering it uncleavable by caspase-2. Slice electrophysiology experiments indicate that caspase-2 cleavage of tau underlies normal and pathological LTD. Whole-cell patch-clamp experiments with cultured neurons containing the human APP gene show normalization of miniature excitatory postsynaptic current frequency and amplitude with the addition of the non-cleavable tau mutation. Our results indicate caspase-2 cleavage of tau is necessary for the accumulation of truncated tau product in neurons, and subsequently synaptic weakening.