It has been demonstrated that the connectivity of hypothalamic feeding circuits is not hard-wired but show predictable changes in response to circulating levels of metabolic hormones. When these dynamic synaptic changes are correlated to behavioral effects of different signals, it becomes clear that evoked synaptic remodeling precedes changes in the behavior of animals. This suggests that synaptic plasticity of hypothalamic circuits governed by peripheral metabolic signals is a pre-requisite to proper behavioral and autonomic adaptations to the changing peripheral milieu.
In the last years, our understanding of glial cell function in the brain has evolved significantly. Their role in various aspects of control of neuronal circuits have been recognized. Astrocytes specifically have been tied to both pre- and post-synaptic control of neuronal transmission via multimodal action. In the hypothalamus, astrocytes and microglia regulate synaptic input organization and activity of neuronal circuits affecting feeding, energy and glucose metabolism. It has been shown that hypothalamic neurons can directly stimulate neighboring astrocytes unmasking a neuron-to-astrocyte communication in the physiological adaptations to changing energetic status.
Our main goal is to identify the different mechanisms underlying the hypothalamic neuron-glia communication implicated in the control of feeding behaviors.
Behavioral test, Electron microscopy, Electrophysiology, immunohistochemistry, stereotaxic delivery of AAvs, genetic mouse models of obesity, molecular biology techniques to assess RNA and protein lexpression levels.
CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese miceNature Communications (Nov, 2023) DOI: 10.1038/s41467-023-42595-7
Paraventricular glia drive circuit function to control metabolismCell Metabolism (Oct, 2022) DOI: 10.1016/j.cmet.2022.09.012