Andrew Lutas, Ph.D., Stadtman Tenure-Track Investigator
- Instructor of Medicine, Harvard Medical School, 2020-2022
- Staff Scientist, Beth Israel Deaconess Medical Center, 2020-2022
Postdoctoral Fellow, Beth Israel Deaconess Medical Center, 2015-2020
Ph.D., Harvard University, 2015
B.S., The Pennsylvania State University, 2008
The purpose of our research is to understand principles of neuromodulation of brain circuits that control motivation and uncover treatment strategies for obesity and comorbid diseases.
Environmental, stressful, and emotional triggers can powerfully impact our food consumption making it difficult to prevent overeating. We study how neural circuits integrate hormonal, neuropeptide, and monoamine neurotransmitter signaling to control the salience of these triggers and influence related processes in energy homeostasis. Our current research is focused on how multiple neuromodulator signals like dopamine and neuropeptides converge on a common intracellular molecular signal, cyclic AMP (cAMP), to adjust neural circuit activity. Studying intracellular signals has been challenging as these signals are difficult to continuously monitor in behaving animals. We overcome these challenges by using optical approaches like two-photon microscopy, novel fluorescent biosensors, and optogenetics to longitudinally track and manipulate molecular signals inside neurons in the intact brain. By combining these optical approaches with behavior tasks and genetic manipulations in rodents, we probe how molecular signals influence the activity of neural circuits involved in the overconsumption of food. We track these intracellular signals with subcellular resolution as they change over the course of daily food consumption and over many weeks of overconsumption leading to obesity.
- History-dependent dopamine release increases cAMP levels in most basal amygdala glutamatergic neurons to control learning.
- Lutas A, Fernando K, Zhang SX, Sambangi A, Andermann ML.
- Cell Rep (2022 Jan 25) 38:110297. Abstract/Full Text
- Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling.
- Zhang SX, Lutas A, Yang S, Diaz A, Fluhr H, Nagel G, Gao S, Andermann ML.
- Nature (2021 Sep) 597:245-249. Abstract/Full Text
Research in Plain Language
Have you ever mindlessly wandered to the kitchen and picked out a tasty snack food to eat? It can be hard to hold back from seeking and eating highly palatable food especially when other factors like context cues, emotions, and stress are involved. In addition, palatable food has rewarding properties that engage the same brain circuits as addictive substances. We research how specialized receptors in the brain influence our motivation to seek and consume palatable food. We also study how neuromodulation influences how we learn associations between stimuli in the world and palatable food. We use microscopy approaches that let us watch how activation of these specialized receptors affect neurons inside the brain. Our goal is to understand how motivation is regulated and discover strategies for treating obesity.