15q11.2-13.1 Duplication (Dup15q) Syndrome is a rare genetic syndrome that results from the duplication of a portion of chromosome 15. Two types of duplications exist: isodicentric duplication (idic) with three copies and interstitial (int) with two copies of the duplicated region. The clinical symptoms in this condition can vary between maternal and paternal duplications with more severe symptoms in maternally derived duplications. These symptoms include hypotonia, motor issues, developmental and speech delays, and sleep issues. Dup15q patients have a high prevalence of autism and about 65-80% have seizures. The 15q region holds genes that are important in early development. This includes UBE3A and multiple gamma-aminobutyric acid type A receptor (GABAAR) genes. We analyzed overnight clinical sleep EEG data recorded using a standard 10-20 montage, 21-channel recording setup. 24-hour EEG recordings from Dup15 mice and WT littermate controls were collected and scored in 10-second epochs. The presence of spikes in sleep EEG was scored and analyzed using MATLAB and Graph Prism. Previous electrophysiological (EEG) studies in the lab found that patients diagnosed with Dup15q showed increased beta band EEG oscillations during wakefulness and sleep. Patients also had reduced spindles and slow wave sleep during the night, disrupting NREM sleep. These can worsen behavioral symptoms as sleep is essential for overall brain function and recovery. The presence of seizures can also impact sleep physiology. We investigated the presence of spike waves in EEG data from patients as well as mouse models to understand its impact on sleep and overall development in hopes to inform our understanding of the pathophysiology of Dup15q syndrome as well as the utility of these models in future pharmacological intervention studies.

Foraging theory describes how foragers, or animals seeking food, make decisions. Associated with virtually all decisions that foragers make is a delay, occurring before or after collecting food. These delays may differ greatly, highlighting the importance of efficient decision-making given the limited time animals have for foraging. In this way, decisions foragers make in nature can be viewed as optimization problems which they solve using a cost-benefit analysis. Furthermore, foraging animals can be viewed as economic decision makers that thrive by maximizing benefits and minimizing costs. To explore decision making in animals, pre- and post-reward delay manipulations have been explored famously in the current literature, with significant biases observed during pre-delay, as compared to post-delay manipulations. This suggests a keen sensitivity of animals to pre-delays, and conversely, an insensitivity to post-delays. In this experiment, we used a rat model to explore relative sensitivities to pre- and post-reward delays under a foraging framework. We utilized an open-field arena, allowing rats to roam freely and more closely approximating its natural habitat. Both pre- and post-reward delay groups (n=2 each) were presented with two options simultaneously, each with distinct temporal properties (a short vs. long delay). Both task groups only differed in the temporal placement of the delays, occurring either before (pre-) or after (post-) the reward. We hypothesize that rats would have a higher selection bias towards the shorter delay option, independent of whether it occurred before or after reward delivery.

Paraquat is a herbicide commonly used for grass and weed control. Exposure to paraquat increases oxidative stress, leading to cell damage and death. Persistent paraquat exposure may increase the risk for Parkinson’s disease (PD), resulting in loss of function in the dopamine neuron cells. Because sleep disruption can be an early symptom of neurodegenerative diseases, including PD, we tested whether sleep is altered in fruit flies treated with paraquat. Two lines of wild-type Drosophila melanogaster (Canton-S, Cs, or wild-caught population cage flies, PCF) flies fed paraquat or vehicle control of different concentrations. 2mM of paraquat is considered our chronic pesticide exposure, while 10mM of paraquat is our acute exposure. After three trials, we report that chronically exposed CS flies developed less sleep over time. The acute exposure to CS flies decreased their amount of sleep, but they did not survive past the first day. PCF flies could survive much longer with both chronic and acute levels of pesticides but still showed similar trends of decreased sleep.

Imagine you’re grocery shopping. You may either stay and get all your groceries from one store or drive to different stores with better deals. When deciding, one considers things such as distance between stores or availability of products. Like humans, a foraging animal must decide how long it's worth staying in a patch before moving on. One prominent theoretical model of foraging suggests that tonic levels of dopamine encode the quality of the current foraging environment, with elevated dopamine concentrations associated with more reward-dense surroundings. However, direct tests of this theory in foraging animals are lacking. Thus, the present study investigates the hypothesis that increasing dopamine levels via methamphetamine will cause rats to leave their current patch sooner due to their altered perspective on the environment. We developed a foraging task involving intertemporal decision making such as staying or leaving choices. The apparatus consists of three chambers including two side foraging patches and one middle waiting patch. We manipulated the reward statistics on the task to change the quality of the environment within each behavioral session, which encouraged rats to remain in patches for different time lengths depending on the conditions. Before each session, rats were injected with either methamphetamine or saline to assess how altering dopamine release affected foraging patterns on the task. Results indicate that methamphetamine has a profound effect on rats' movement patterns, causing thigmotaxis. Methamphetamine also caused rats to remain in all patches for shorter durations, consistent with theoretical models of dopamine encoding environment quality.

The medial prefrontal cortex (mPFC) is a critical brain structure that integrates sensory and emotional information to guide adaptive behavior through its various output circuits. mPFC neurons projecting to the basolateral amygdala (BLA) have been shown to promote the expression of active avoidance in adult rats. The mPFC undergoes a prolonged development and mPFC-BLA neurons display functional changes throughout early life. How mPFC-BLA neurons contribute to avoidance behavior in the juvenile period is unknown. We used optogenetic techniques in conjunction with a platform-mediated avoidance assay to study mPFC-BLA circuit function in postnatal day (P)23 (juvenile) mice. Mice were trained with a series of 9 tone-paired foot shocks wherein entrance onto a nearby safely platform allowed avoidance of the shock. The following day, we used laser light to excite or inhibit mPFC-BLA neurons during 6 tone presentations without shocks. When mPFC-BLA neurons were excited, we observed a decrease in avoidance compared to control mice (U = 9.0, p = 0.02). When mPFC-BLA neurons were inhibited, there was no change in avoidance compared to control mice (U = 25.0, p > 0.05). Given that excitation of mPFC-BLA neurons promotes avoidance in adults, this evidence demonstrates age-dependent differences in mPFC control of avoidance behavior. Understanding the progression mPFC circuit maturation will provide a foundation to understand how these circuits are disrupted in psychiatric diseases where avoidance goes awry.