Dr. Yuan received her Ph.D. training from University of Pennsylvania, where she studied the role of serotonergic regulation in circadian rhythms and sleep with Dr. Amita Sehgal. From 2006 to 2012, Dr. Yuan was trained as a postdoctoral fellow at University of California, San Francisco in Dr. Yuh-Nung Jan's laboratory, where she developed a system to study experience-dependent structural and functional plasticity in the Drosophila larval visual circuit. Dr. Yuan joined NINDS as an investigator in 2013. The primary research goal is to identify the cellular and molecular mechanisms underlying the homeostatic regulation of dendrite morphogenesis and structural plasticity, as well as the development and maturation of the central cholinergic synapse.
Proper functions of neuronal circuits rely on the fidelity of their assembly, while adaptive modifications are also essential. Our research objectives are to understand how experience and genetic programming interact to shape the structural and functional connectivity during brain development.
Our work revealed visual experience-induced homeostatic structural plasticity regulating dendrite size in the developing Drosophila larval visual circuit. In contrast to the long-standing belief that the fly brain is hard-wired, our studies illustrated striking homeostatic structural adaptations that contribute to the regulation of dendrite development. Conceptually similar to the homeostatic regulation of synaptic strength and efficacy, homeostatic structural plasticity demonstrates a persistent impact on neuronal intrinsic excitability and circuit properties but remains largely uncharacterized. Taking advantage of the exceptional optical and genetic accessibility of the larval visual circuit, we performed large scale genetic screens and analyzed candidate genes using in vivo imaging studies. In combination with cell-specific RNA-seq analyses and optical functional recordings, our genetic studies offer insights into the cellular and molecular mechanisms underlying structural plasticity during development.
The Drosophila system allows rapid identification and systematic analyses of novel molecular pathways using anatomical, physiological and behavioral approaches. Currently, we are performing experiments to: identify the molecular machinery regulating dendrite morphogenesis and structural plasticity; determine cellular mechanisms mediating visually-guided behaviors in Drosophila larvae; and investigate the functional consequences of deficits in homeostatic neuronal plasticity.
Jun Yin, PhD, Research Fellow
Hsueh-Ling (Charlene) Chen, PhD, Postdoctoral Fellow
Justin Rosenthal, Graduate Student
Jacob Short, Lab Manager
Jingce Lei, Postbac Fellow
Anna Grigsby-Brown, Postbac Fellow
Caixia Long, Biologist
- Rosenthal JS, Yin J, Lei J, Short J, Long C, Spillman E, Sheng C, Yuan Q. Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development. Proceedings of the National Academy of Sciences Jun 2021, 118 (23) e2004685118.
- Yin J, Spillman E, Cheng ES, Short J, Chen Y, Lei J, Gibbs M, Rosenthal JS, Sheng C, Chen Y, Veerasammy K, Choetso T, Abzalimov R, Wang B, Han C, He Y, Yuan Q. Brain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling. Nature Communications. 2021; 12: 2408.
- Qin B, Humberg T*, Kim A*, Kim HS, Short J, Diao F, White BH, Sprecher SG, Yuan Q. Muscarinic acetylcholine receptor signaling generates OFF selectivity in a simple visual circuit. Nature Communications. 2019; 10: 4093.
- Dombrovski M, Kim A, Poussard L, Vaccari A, Acton S, Spillman E, Condron B*, Yuan Q*. A Plastic visual pathway regulates cooperative behavior in Drosophila larvae. Current Biology. 2019 Jun 3;29(11):1866-1876.
- Yin J, Gibbs M, Long C, Rosenthal J, Kim HS, Kim A, Sheng C, Ding P, Javed U, Yuan Q. Transcriptional regulation of lipophorin receptors supports neuronal Adaptation to chronic elevations of activity. Cell Reports. 2018; 25(5):1181-1192.
- Sheng C, Javed U, Gibbs M, Long C, Yin J, Qin B, Yuan Q. Experience-dependent structural plasticity targets dynamic filopodia in regulating dendrite maturation and synaptogenesis. Nature Communications. 2018; 9(1):3362.