The Bocarsly Lab uses a systems level approach to identify the neural substrates, circuits, and behavioral motivations driving food intake and their contributions to the development of disease states such as compulsive overeating, obesity, and anorexia. To do this, the laboratory uses a combination of novel transgenic mouse lines, optogenetics, chemogenetics, in vivo fiber photometry, molecular techniques, ex vivo brain slice fast-scan cyclic voltammetry, and fiber photometry, as well as behavior using mouse models.
Central Insulin Sensitivity Augmented by Semaglutide in Obese Male Mice
GLP-1 receptor agonist semaglutide has been shown to regulate feeding behaviors for substantial weight loss. Treated patients and animal models demonstrate changes in the regulation of dopamine transmission in the striatum. We are investigating insulin signaling as a mechanism for central satiation signaling in the dorsal and ventral striatum through increased evoked dopamine concentrations.
Neurochemical effects of in a high-risk schizophrenia mouse model
Schizophrenia affects 1% of the world's population with no known etiology as of date . As a debilitating disease hypothesized to be connected dopamine dysregulation in the striatum, this project aims to elucidate the neurochemical and signaling changes of dopamine in this model. Furthermore, using chronic treatment of select antipsychotics we are looking at drug induced modifications to this pathway.
Characterizing the neural circuitry modulating reward-based overeating behaviors in an "overconsumption prone" mouse model
Reward-based overeating, a maladaptive feeding pattern characterized by hedonic compulsive overconsumption, involves dysregulation of feeding and reward processing and may be contributing to the increased prevalence of obesity. Modeling reward-based overeating in mice allows for investigation of this feeding pattern and the development of an "overconsumption prone" mouse model that is predisposed to reward-based overeating. Defining the neural circuitry and characterizing the behaviors and neurochemistry of animals predisposed to reward-based overeating allows for identification of potential targets in intervention to treat or prevent obesity.
Dopamine D3 receptors in the striatum and their involvement in behaviors in obesity and addiction
Using novel transgenic mice, stereotaxic surgery, and behavioral interventions we are evaluating the role of the dopamine D3 receptor and its role in obesity and addiction phenotypes. Through further investigation we hope to elucidate the effect that the D3R plays in these behaviors and contribute towards future interventions.
The role of high-fat diet consumption on emotion like-behaviors and dopamine circuitry in the amygdala
This project utilizes animal models to examine the link between dietary fat intake and the development of mental health disorders with the goal of elucidating neuronal circuitry in the amygdala. We are using behavioral assessments, voltammetry, chemogenetics tools, qPCR, and ELISA assays.
Evaluating the Role of ApoE4 on Insulin Resistance in Alzheimer’s Disease
Alzheimer’s disease is the most common neurodegenerative disorder, and the apolipoprotein E4 (ApoE4) allele has been identified as the strongest genetic risk factor for AD. The scope of ApoE4's contribution to Alzheimer's remains unclear, but research suggests that it may cause impaired neuronal insulin signaling and insulin resistance. Using both in-vitro and in-vivo studies, we investigate the role of ApoE4 in Alzheimer's pathology by determining its impact on insulin signaling and identifying possible therapeutic strategies.
Dopamine D2 receptors in the lateral hypothalamus and their role in dysregulated feeding
Obesity poses a growing public health issue, and it is becoming increasingly evident that this addictive state of eating may be associated with dysregulation in dopaminergic reward pathways. Using transgenic mice and stereotaxic surgery, we investigate the role of the dopamine D2 receptor in the lateral hypothalamus, the "feeding center" of the brain.
Exploring neurological contributors driving the comorbidity between alcohol use disorder and binge eating disorder
Studies indicate people with binge eating disorder (BED) are 1.5 times more likely to develop alcohol use disorder (AUD) than those without. More broadly, around 25% of individuals suffering from BED report a co-occurring substance use disorder however the exact neural underpinnings of this relationship is still unknown. By modeling a binge prone"