Tionna Ouellette

Using mouse models to understand how glia-neuron interactions in the hypothalamus control sensation of hunger, food intake, and body weight.

Glia-Neuron interactions as drivers of behavioral output. Glial cells like Astrocytes were once thought to be supportive cells in the CNS with less influence over behavior than their electrically active counterparts, neurons. Astrocytes are now more widely appreciated for their role in shaping neuronal output and influencing behavior. Astrocytes have an abundance of functions including maintenance of the blood brain barrier, buffering ions from the synapse, providing metabolic support to neurons, and signaling to neurons via gliotransmitters that affect output. This complexity allows astrocytes to be highly specialized to a location, creating regional heterogeneity in the population. There are several areas of the brain for which we do not fully understand how or if astrocytes contribute to neuronal function and behavior.

Disease Model: Diet-Induced Obesity. Increasing prevalence of and healthcare costs associated with obesity and type two diabetes, combined with increasing cultural awareness around food quality and diet patterns, highlight the need for further research on CNS contribution to food intake behaviors. The hypothalamus is the control center for feeding in the brain, with the critical neural population being AgRP neurons in the Arcuate Nucleus. Dysregulation of AgRP neuronal firing patterns contributes to excess food intake and development of diet induced obesity in the mouse model, but the mechanism for this is poorly understood. It was previously documented that hypothalamic astrocytes dynamically change contact with AgRP neurons in the fed and overnight fasted states of healthy mice to regulate firing patterns, but we do not know how these cell types interact under a high fat diet condition. Additionally, while we know that astrocytes in the obese animals are reactive, we do not know when this begins, and if or how it affects the changing AgRP neuronal firing rate seen in animals on a high fat diet.

The goal of my thesis project is to characterize hypothalamic astrocyte morphology and physiology with exposure to high fat diet and determine if the observed dysregulation is causal to AgRP neuronal dysfunction seen in the Died-Induced Obesity mouse model.

Tionna Ouellette on ORCID