Scientist, Vollum Institute
Haining Zhong earned his B.A. in Biological Science and Biotechnology, and B.Eng. in Electronics and Computer Science from Tsinghua University in Beijing, China in 1996. He received his Ph.D. in Neuroscience from the Johns Hopkins University School of Medicine in 2002. Zhong did postdoctoral training at the Cold Spring Harbor Laboratory and then at the Janelia Farm Research Campus of the Howard Hughes Medical Institute. In 2009 he was appointed as an assistant scientist at the Vollum Institute and was promoted to scientist in 2015.
Summary of current research
We study how the brain is regulated and changed to allow the animal to adapt to and excel in the ever-changing world. Our focus is on two types of regulations — neuromodulation and experience-dependent plasticity — using rodents as the experimental model. We harness the advantages of both in vitro and in vivo experiments depending on the specific question using a variety of approaches, including advanced microscopy, electrophysiology, optogenetics, mouse genetics, CRISPR-based gene editing, and computation. Because novel technology enables us to ask long standing questions in new ways, we also actively adapt and develop the relevant technologies, such as endogenous protein labeling, biosensors for subcellular signaling pathways and microscopy.
We have openings for highly motivated students and postdocs who are interested in these directions. Please contact Haining Zhong directly at firstname.lastname@example.org for more information.
Neuromodulation impinges powerful control over brain function and mediates the switch between different biological states: fight/flight, sleep/awake, attention, reward, stress, locomotion, etc. Defective neuromodulation has been linked to many neurological disorders and neurodegenerative diseases, such as schizophrenia, bipolar disorder and Parkinson’s disease.
- Dissect neuromodulatory function during animal behavior using advanced microscopy combined with novel genetically-encoded sensors we developed to monitor events downstream of neuromodulation
- Expand development of microscopic techniques that allow faster imaging and which are easier to use and compatible with free-moving animal behaviors
- Develop novel fluorescence sensors for imaging intracellular processes in response to diverse neurotransmitters
Experience-dependent plasticity of brain circuits underlies learning and memory.
- Generate genetically modified mice to visualize protein organization and dynamics in vivo as readout for neuronal properties, connectivity and plasticity
- Explore how animal behaviors alter synaptic connectivity and strength
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. Watch the video article at JoVE
Patriarchi T, Cho JR, Merten K, Howe MW, Marley A, Xiong WH, Folk RW, Broussard GJ, Liang R, Jang MJ, Zhong H, Dombeck D, von Zastrow M, Nimmerjahn A, Gradinaru V, Williams JT, Tian L. (2018) Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science 360:eaat4422.
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
Tillo SE, Xiong WH, Takahashi M, Miao S, Andrade AL, Fortin DA, Yang G, Qin M, Smoody BF, Stork PJS, Zhong H. (2017) Liberated PKA catalytic subunits associate with the membrane via myristoylation to preferentially phosphorylate membrane substrates. Cell Reports 19:617-629.
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.
Zhong H. (2015) Applying superresolution localization-based microscopy to neurons. Synapse 69:283-294.
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
Zhong H. (2010) Photoactivated localization microscopy (PALM): an optical technique for achieving ~10-nm resolution. Cold Spring Harb. Protoc. 2010(12):pdb.top91.
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.
Do MT, Kang SH, Xue T, Zhong H, Liao HW, Bergles DE, Yau KW. (2009) Photon capture and signaling by melanopsin retinal ganglion cells. Nature 457:281-287.
Ji N, Shroff H, Zhong H, Betzig E. (2008) Advances in the speed and resolution of light microscopy. Curr. Opin. Neurobiol. 18:605-616.
Harvey CD, Yasuda R, Zhong H, Svoboda K. (2008) The spread of Ras activity triggered by activation of a single dendritic spine. Science 321:136-140.
Yasuda R, Harvey CD, Zhong H, Sobczyk A, van Aelst L, Svoboda K. (2006) Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nature Neurosci. 9:283-291.
Fu Y, Zhong H, Wang MH, Luo DG, Liao HW, Maeda H, Hattar S, Frishman LJ, Yau KW. (2005) Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin. Proc. Natl. Acad. Sci. USA 102:10339-10344.
Zhong H, Lai J, Yau KW. (2003) Selective heteromeric assembly of cyclic nucleotide-gated channels. Proc. Natl. Acad. Sci. USA 100:5509-5513.
Zhong H, Molday LL, Molday RS, Yau KW. (2002) The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420:193-198.
Munger SD, Lane AP, Zhong H, Leinders-Zufall T, Yau KW, Zufall F, Reed RR. (2001) Central role of the CNGA4 channel subunit in Ca2+-calmodulin-dependent odor adaptation. Science 294:2172-2175.
Grunwald ME, Zhong H, Lai J, Yau KW. (1999) Molecular determinants of the modulation of cyclic nucleotide-activated channels by calmodulin. Proc. Natl. Acad. Sci. USA 96:13444-13449.