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. Our 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, we aim to understand how the dynamics of neuromodulators and intracellular signals contribute to the function of neuromodulators, to learning, and to the function of sleep. We combine 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. Our 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 (PKI). In Press. Frontiers in Pharmacology. bioRxiv doi:https://doi.org/10.1101/2020.11.25.399204 *Co-corresponding authors.
- Lee SJ, Lodder B, Chen Y, Patriarchi T, Tian L, Sabatini BL (2020). Cell-type-specific asynchronous modulation of PKA by dopamine in learning. Nature Online ahead of print.
- Chen Y, Granger AJ, Tran T, Saulnier JL, Kirkwood A, Sabatini BL (2017). Endogenous Gαq-coupled neuromodulator receptors activate protein kinase A. Neuron 96: 1070.
- Chen Y, Saulnier JL, Yellen G, Sabatini BL (2014). A PKA activity sensor for quantitative analysis of endogenous GPCR signaling via 2-photon FRET-FLIM imaging. Frontiers in Pharmacology 5: 56.
- Chen Y, Mohammadi M, Flanagan JG (2009). Graded levels of FGF protein span the midbrain and can instruct graded induction and repression of neural mapping labels. Neuron 62: 773-780.
For a complete list of Dr. Chen's publications, click here.