Tianyi Mao, Ph.D.
Scientist, Vollum Institute
After earning her B.S. in Biological Science and Biotechnology at Tsinghua University in Beijing, China in 1997, Mao received her Ph.D. in Neuroscience from the Johns Hopkins University School of Medicine in 2005. She did postdoctoral research at the Cold Spring Harbor Laboratory and then at the Howard Hughes Medical Institute's Janelia Farm Research Campus. Mao was appointed as an assistant scientist at the Vollum Institute in September 2010 and was promoted to scientist in 2017.
Summary of current research
The basal ganglia are critical for many fundamental brain functions, such as movement control and decision-making. Dysfunction of the basal ganglia contributes to the pathophysiology of many neurodegenerative diseases, most notably Parkinson's disease and Huntington's disease. Our understanding of the basal ganglion has been limited by the complexity of the circuitry. For example, increasing evidence suggests that neurons in the basal ganglia are heterogeneous, yet little is known about the anatomical and functional connectivity of individual cell types.
In my laboratory, we examine the functional connectivity within basal ganglia and its interaction with cerebral cortex and thalamus. We target defined cell types by combining novel functional circuit analysis tools and molecular genetic technology with classical anatomical tracing. We also use two-photon imaging with genetically encoded calcium sensors to study the signal transduction events in basal ganglia that underlie the dynamics of functional circuitry.
Alterations in basal ganglia circuits also are associated with behavioral perturbations in drug addiction and neurodegenerative diseases. A mid-term goal of our research program is to investigate how the circuitry changes during different behaviors (e.g. goal-directed vs. habitual), and in animal models of addiction.
These projects are expected to be synergistic. With these complementary approaches, we aim to determine the cell-type specific circuitry, a prerequisite for a mechanistic understanding of basal ganglia function in health and disease.
Learn more about Dr. Mao's research in this Research Week 2017 interview
Massengill CI, Bayless-Edwards L, Ceballos CC, Cebul ER, Qin M, Whorton MR, Ye B, Mao T*, Zhong H*. (2021) Highly sensitive genetically-encoded sensors for population and subcellular imaging of cAMP in vivo. bioRxiv Aug 28; https://doi.org/10.1101/2021.08.27.457999 *Corresponding authors
Ma L, Day-Cooney J, Benavides OJ, Muniak MA, Qin M, Ding JB, Mao T#, Zhong H#. (2022) Locomotion activates PKA through dopamine and adenosine in striatal neurons. *Co-first Authorships. #Co-senior Authorships. Nature. Nov;611(7937):762-768. doi: 10.1038/s41586-022-05407-4. Epub 2022 Nov 9. PMID: 36352228.
Massengill CI*, Bayless-Edwards L*, Ceballos CC, Cebul ER, Cahill J, Bharadwaj A, Wilson E, Qin M, Whorton MR, Baconguis I, Ye B, Mao T, Zhong H. (2022) Sensitive genetically encoded sensors for population and subcellular imaging of cAMP in vivo. Nat Methods. Nov;19(11):1461-1471. doi: 10.1038/s41592-022-01646-5. Epub 2022 Oct 27. PMID: 36303019.
Wilson EA, Mao T, Zhong H. (2022) Labeling Endogenous Proteins Using CRISPR-mediated Insertion of Exon (CRISPIE). Bio Protoc. Mar 5;12(5):e4343. doi: 10.21769/BioProtoc.4343. eCollection 2022 Mar 5. PMID: 35592602.
Day-Cooney J, Dalangin R, Zhong H#, Mao T#. (2023) Genetically encoded fluorescent sensors for imaging neuronal dynamics in vivo. #Co-senior Authorships. J Neurochem. Feb;164(3):284-308. doi: 10.1111/jnc.15608. Epub 2022 Apr 9. PMID: 35285522.
Melander JB*, Nayebi A*, Jongbloets BC, Fortin DA, Maozhen Q, Ganguli S#, Mao T#, Zhong H#. (2021) Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons. *Contributed equally. #Co-correspondence. Cell Reports.
Melander JB, Nayebi A, Jongbloets BC, Fortin DA, Qin M, Ganguli S*, Mao T*, Zhong H*. (2021) Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and inhibitory interneurons. *Corresponding authors. Cell Reports, In press.
Massengill CI, Day-Cooney J, Mao T, Zhong H. (2021) Genetically encoded sensors towards imaging cAMP and PKA activity in vivo. J. Neurosci. Methods 362:109298.
Zhong H, Ceballos CC, Massengill CI, Muniak MA, Ma L, Qin M, Petrie SK, Mao T. (2021) High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion. eLife Jun 8; 10:e64911.
Jongbloets BC, Ma L, Mao T, Zhong H. (2019) Visualizing Protein Kinase A activity in head-fixed behaving mice using in vivo two-photon fluorescence lifetime imaging microscopy. J. Vis. Exp. Jun 7; (148) doi: 10.3791/59526.
Birdsong WT, Jongbloets BC, Engeln KA, Wang D, Scherrer G, Mao T. (2019) Synapse-specific opioid modulation of thalamo-cortico-striatal circuits. Elife 8:e45146.
Ma L, Jongbloets BC, Xiong WH, Melander JB, Qin M, Lameyer TJ, Harrison MF, Zemelman BV, Mao T*, Zhong H*. (2018) A highly sensitive A-kinase activity reporter for imaging neuromodulatory events in awake mice. Neuron 99:665-679.e5. *Co-senior authorship
Jongbloets BC, Lemstra S, Schellino R, Broekhoven MH, Parkash J, Hellemons AJ, Mao T, Giacobini P, van Praag H, De Marchis S, Ramakers GM, Pasterkamp RJ. (2017) Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors. Nature Commun. 8:14666.
Shi W, Xianyu A, Han Z, Tang X, Li Z, Zhong H, Mao T, Huang K, Shi SH. (2017) Ontogenetic establishment of order-specific nuclear organization in the mammalian thalamus. Nature Neurosci. 20:516-528.
Hunnicutt BJ, Jongbloets BC, Birdsong WT, Gertz KJ, Zhong H, Mao T. (2016) A comprehensive excitatory input map of the striatum reveals novel functional organization. Elife 5:e19103.
Fortin DA, Tillo SE, Yang G, Rah JC, Melander JB, Bai S, Soler-Cedeño O, Qin M, Zemelman BV, Guo C, Mao T*, Zhong H*. (2014) Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins. J. Neurosci. 34:16698-16712. *Co-senior authorship
Hunnicutt BJ, Long BR, Kusefoglu D, Gertz KJ, Zhong H*, Mao T*. (2014) A comprehensive thalamocortical projection map at the mesoscopic level. Nature Neurosci. 17:1276-1285. *Co-senior authorship
Hooks BM, Mao T, Gutnisky DA, Yamawaki N, Svoboda K, Shepherd GM. (2013) Organization of cortical and thalamic input to pyramidal neurons in mouse motor cortex. J. Neurosci. 33:748-760.
Madisen L, Mao T, Koch H, Zhuo JM, Berenyi A, Fujisawa S, Hsu YW, Garcia AJ 3rd, Gu X, Zanella S, Kidney J, Gu H, Mao Y, Hooks BM, Boyden ES, Buzsáki G, Ramirez JM, Jones AR, Svoboda K, Han X, Turner EE, Zeng H. (2012) A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat. Neurosci. 15:793-802.
Mao T, Kusefoglu D, Hooks BM, Huber D, Petreanu L, Svoboda K. (2011) Long-range neuronal circuits underlying the interaction between sensory and motor cortex. Neuron 72:111-123.
Lewis TL Jr, Mao T, Arnold DB. (2011) A role for myosin VI in the localization of axonal proteins. PLoS Biol. 9:e1001021.
Pan WX, Mao T, Dudman JT. (2010) Inputs to the dorsal striatum of the mouse reflect the parallel circuit architecture of the forebrain. Front. Neuroanat. 4:147.
Tian L, Hires SA, Mao T, Huber D, Chiappe ME, Chalasani SH, Petreanu L, Akerboom J, McKinney SA, Schreiter ER, Bargmann CI, Jayaraman V, Svoboda K, Looger LL. (2009) Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nature Methods 12:875-881.
Zhong H, Sia GM, Sato TR, Gray NW, Mao T, Khuchua Z, Huganir RL, Svoboda K. (2009) Subcellular dynamics of type II PKA in neurons. Neuron 62:363-374.
Lewis TL Jr, Mao T, Svoboda K, Arnold DB. (2009) Myosin-dependent targeting of transmembrane proteins to neuronal dendrites. Nature Neurosci. 12:568-576.
Petreanu L, Mao T, Sternson SM, Svoboda K. (2009) The subcellular organization of neocortical excitatory connections. Nature 457:1142-1145.
Mao T, O'Connor DH, Scheuss V, Nakai J, Svoboda K. (2008) Characterization and subcellular targeting of GCaMP-type genetically-encoded calcium indicators. PLoS One 3:e1796.