Neuromodulators such as dopamine, acetylcholine, and neuropeptides have profound effects on neural circuits and behavior. Altered neuromodulation is associated with most psychiatric disorders, major neurodegenerative disorders, and neuromodulatory systems are targets of almost all drugs of abuse. While specific behaviors have been linked to specific neuromodulators, and while many neuromodulator receptors and their downstream signaling pathways are known, how neuromodulators regulate behavior remains enigmatic.
The knowledge gap exists because our understanding of molecular signaling networks remains largely a static diagram of connections between molecules. The Chen laboratory attempts to fill the gap between molecular neuroscience and animal behavior by elucidating the spatial and temporal dynamics of biological signals, because their dynamics carry critical information that explain subsequent modifications of cells, circuits, and behavior.
Specifically, the lab aims to understand how the dynamics of neuromodulators and intracellular signals contribute to the function of neuromodulators, to learning, and to the function of sleep. The lab combines biosensor development, two photon fluorescence lifetime imaging microscopy, electrophysiology, as well as molecular, cellular, and biochemical approaches in mice to visualize molecular dynamics in action, perturb them with precise spatiotemporal control, and analyze the functional consequences. This research promises to uncover principles of neuromodulator action, illuminate how molecular mechanisms produce behaviorally relevant features, and ultimately help treat psychiatric disorders.
- Chen Y*, Sabatini BL*. The kinase specificity of protein kinase inhibitor peptide. (2021) Frontiers in Pharmacology. 2021; 12:632815. *Co-corresponding authors.
- Lee SJ, Lodder B, Chen Y, Patriarchi T, Tian L, Sabatini BL. Cell-type-specific asynchronous modulation of PKA by dopamine in learning. Nature. 2021; 590(7846): 451-456. doi: 10.1038/s41586-020-03050-5. Epub Dec 23, 2020.
- Chen Y, Granger AJ, Tran T, Saulnier JL, Kirkwood A, Sabatini BL. Endogenous Gαq-coupled neuromodulator receptors activate protein kinase A. Neuron. 2017; 96:1070.
- Chen Y, Saulnier JL, Yellen G, Sabatini BL. A PKA activity sensor for quantitative analysis of endogenous GPCR signaling via 2-photon FRET-FLIM imaging. Frontiers in Pharmacology. 2017; 5:56.
- Chen Y, Mohammadi M, Flanagan JG. Graded levels of FGF protein span the midbrain and can instruct graded induction and repression of neural mapping labels. Neuron. 2009; 62: 773-780.
See a complete list of Dr. Chen’s publications on PubMed.
2009, PhD, Cell and Developmental Biology, Harvard University
2002, BA Honors, Natural Sciences, Cambridge University
2020-2022 NARSAD Young Investigator Award, Brain and Behavior Grant
2019-2022 Whitehall Foundation Research Grant
2014-2016 Ruth L. Kirschstein NRSA Individual Postdoctoral Fellowship from the NIH
2009 Anuradha Rao Memorial Travel Award from the Rao family and Neuron
2004 Harvard University Certificate of Distinction in Teaching