Team

Staff Profiles

Hongkui Zeng, Ph.D.

Executive Director, Structured Science

hongkuiz@alleninstitute.org

Hongkui Zeng joined the Allen Institute for Brain Science in 2006. She currently leads the Structured Science Division to develop and operate high-throughput pipelines to generate large-scale, open-access datasets and tools to accelerate neuroscience discovery. Since joining the Allen Institute, she has also led several research programs, including the Transgenic Technology program, the Human Cortex Gene Survey project, the Allen Mouse Brain Connectivity Atlas project, and the Mouse Cell Types and Connectivity program. Zeng received her Ph.D. in molecular and cell biology from Brandeis University, where she studied the molecular mechanisms of the circadian clock in fruit flies. Then as a postdoctoral fellow at Massachusetts Institute of Technology, she studied the molecular and synaptic mechanisms underlying hippocampus-dependent plasticity and learning. Her current research interests are in understanding neuronal diversity and connectivity in the mouse visual cortical circuit and how different neuronal types work together to process and transform visual information. She has broad scientific experience and a keen interest in using a combined molecular, anatomical and physiological approach to unravel mechanisms of brain circuitry and potential means for treating brain diseases.

Research

Research Interests

The brain circuit is an intricately interconnected network of a vast number of neurons with diverse molecular, anatomical and physiological properties. To understand the principles of information processing in the brain circuit, it is essential to have a systematic understanding of the common and unique properties for each of its components - the neuronal cell types, to monitor their activities while the brain is processing information, and to have the ability to manipulate these neurons to investigate their functions in the brain circuit. Combining genetic tools with large-scale imaging and single-cell analysis technologies presents us with the opportunity to gain systematic understanding of the properties, interconnections and functions of these cell types. My team at the Allen Institute for Brain Science has been building multiple platforms, including single-cell transcriptomics, single and multi-patching electrophysiology, 3D reconstruction of neuronal morphology, high throughput brain-wide connectivity mapping, neuronal activity imaging, and cell type-targeted transgenic and viral to characterize the transcriptomic, physiological, morphological, and connectional properties of different types of neurons in a standardized way, towards a taxonomy of cell types and a description of their connectivity matrix for mouse brain circuits such as the visual cortico-thalamic system. Building such knowledge base lays the foundation towards the understanding of the computational mechanisms of brain circuit function.

Expertise

  • Molecular neuroscience
  • Genetics
  • Neuroanatomy
  • Behavior

Research Programs

  • Cell Types
  • Connectivity
  • Atlasing

Selected Publications View on PUBMED

Visual Cortex Gains Independence from Peripheral Drive before Eye Opening

Neuron
September 24, 2019

Gribizis A, Ge X, Daigle TL, Ackman JB, Zeng H, Lee D, Crair MC

Conserved cell types with divergent features in human versus mouse cortex

Nature
August 21, 2019

Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT, Close JL, Long B, Johansen N, Penn O, Yao Z, Eggermont J, Höllt T, Levi BP, Shehata SI, Aevermann B, Beller A, Bertagnolli D, Brouner K, Casper T, Cobbs C, Dalley R, Dee N, Ding SL, Ellenbogen RG, Fong O, Garren E, Goldy J, Gwinn RP, Hirschstein D, Keene CD, Keshk M, Ko AL, Lathia K, Mahfouz A, Maltzer Z, McGraw M, Nguyen TN, Nyhus J, Ojemann JG, Oldre A, Parry S, Reynolds S, Rimorin C, Shapovalova NV, Somasundaram S, Szafer A, Thomsen ER, Tieu M, Quon G, Scheuermann RH, Yuste R, Sunkin SM, Lelieveldt B, Feng D, Ng L, Bernard A, Hawrylycz M, Phillips JW, Tasic B, Zeng H, Jones AR, Koch C, Lein ES

TeraVR empowers precise reconstruction of complete 3-D neuronal morphology in the whole brain

Nature Communications
August 2, 2019

Wang Y, Li Q, Liu L, Zhou Z, Ruan Z, Kong L, Li Y, Wang Y, Zhong N, Chai R, Luo X, Guo Y, Hawrylycz M, Luo Q, Gu Z, Xie W, Zeng H, Peng H

Classification of electrophysiological and morphological neuron types in mouse visual cortex

Nature Neuroscience
June 17, 2019

Gouwens NW, Sorensen SA, Berg J, Lee C, Jarsky T, Ting J, Sunkin S, Feng D, Anastassiou C, Barkan E, Bickley K, Blesie N, Braun T, Brouner K, Budzillo A, Caldejon S, Casper T, Castelli D, Chong P, Crichton K, Cuhaciyan C, Daigle T, Dalley R, Dee N, Desta T, Dingman S, Doperalski A, Dotson N, Egdorf T, Fisher M, de Frates RA, Garren E, Garwood M, Gary A, Gaudreault N, Godfrey K, Gorham M, Gu H, Habel C, Hadley K, Harrington J, Harris J, Henry A, Hill D, Josephsen S, Kebede S, Kim L, Kroll M, Lee B, Lemon T, Liu X, Long B, Mann R, McGraw M, Mihalas S, Mukora A, Murphy GJ, Ng L, Ngo K, Nguyen TN, Nicovich PR, Oldre A, Park D, Parry S, Perkins J, Potekhina L, Reid D, Robertson M, Sandman D, Schroedter M, Slaughterbeck C, Soler-Llavina C, Sulc J, Szafer A, Tasic B, Taskin N, Teeter C, Thatra N, Tung H, Wakeman W, Williams G, Young R, Zhou Z, Farrell C, Peng H, Hawrylycz MJ, Lein E, Ng L, Arkhipov A, Bernard A, Phillips J, Zeng H, Koch C

Neuronal cell-subtype specificity of neural synchronization in mouse primary visual cortex

Nature Communications
June 10, 2019

Knoblich U, Huang L, Zeng H, Li L

Volumetric Ca2+ Imaging in the Mouse Brain Using Hybrid Multiplexed Sculpted Light Microscopy

Cell
April 11, 2019

Weisenburger S, Tejera F, Demas J, Chen B, Manley J, Sparks FT, Martínez Traub F, Daigle T, Zeng H, Losonczy A, Vaziri A

Autonomous patch clamp robot for functional characterization of neurons in vivo: development and application to mouse visual cortex

Journal of Neurophysiology
April 10, 2019

Holst G, Stoy WA, Yang B, Kolb I, Kodandaramaiah SB, Li L, Knoblich U, Zeng H, Haider B, Boyden ES, Forest CR

In vivo sub-millisecond two-photon optogenetics with temporally focused patterned light

Journal of Neuroscience
March 4, 2019

Chen IW, Ronzitti E, Lee BR, Daigle T, Dalkara D, Zeng H, Emiliani V, Papagiakoumou E

A gut-to-brain signal of fluid osmolarity controls thirst satiation

Nature
March 27, 2019

Zimmerman CA, Huey EL, Ahn JS, Beutler LR, Tan CL, Kosar S, Bai L, Chen Y, Corpuz TV, Madisen L, Zeng H, Knight ZA

Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Proceedings of the National Academy of Sciences
March 21, 2019

Lo L, Kim D, Yao S, Cetin A, Harris JA, Zeng H, Anderson DJ, Weissbourd B

Epigenetic landscape and AAV targeting of human neocortical cell classes

bioRxiv
February 19, 2019

Mich JK, Hess EE, Graybuck LT, Somasundaram S, Miller JA, Ding Y, Shapovalova NV, Fong O, Yao S, Mortrud M, Chong P, Bertagnolli D, Goldy J, Casper T, Kroll M, Hodge RD, Bakken TE, Yao Z, Dee N, Cetin A, Smith KA, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Keene CD, Silbergeld DL, Gradinaru V, Sunkin SM, Zeng H, Lein ES, Tasic B, Ting JT, Levi BP

Intersectional monosynaptic tracing for dissecting subtype-specific organization of GABAergic interneuron inputs

Nature Neuroscience
January 28, 2019

Yetman MJ, Washburn E, Hyun JH, Osakada F, Hayano Y, Zeng H, Callaway EM, Kwon HB, Taniguchi H

Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex

bioRxiv
January 13, 2019

Smith SJ, Sumbul U, Graybuck LT, Collman F, Sharmishtaa S, Gala R, Gliko O, Elabbady L, Miller J, Bakken T, Yao Z, Lein ES, Zeng H, Tasic B, Hawrylycz M

Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior

Cell
October 17, 2019

Kim DW, Yao Z, Graybuck LT, Kim TK, Nguyen TN, Smith KA, Fong O, Yi L, Koulena N, Pierson N, Shah S, Lo L, Pool AH, Oka Y, Pachter L, Cai L, Tasic B, Zeng H, Anderson DJ

Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes

Scientific Reports
September 28, 2018

Shahbazi A, Kinnison J, Vescovi R, Du M, Hill R, Joesch M, Takeno M, Zeng H, da Costa NM, Grutzendler J, Kasthuri N, Scheirer WJ

Sparse recurrent excitatory connectivity in the microcircuit of the adult mouse and human cortex

eLife
September 26, 2018

Seeman SC, Campagnola L, Davoudian PA, Hoggarth A, Hage TA, Bosma-Moody A, Baker CA, Lee, JH, Mihalas S, Teeter C, Ko AL, Ojemann JG, Gwinn RP, Silbergeld DL, Cobbs C, Phillips J, Lein E, Murphy G, Koch C, Zeng H, Jarsky T

Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient

Nature Cell Biology
July 23, 2018

Beumer J, Artegiani B, Post Y, Reimann F, Fiona Gribble, Nguyen TN, Zeng H, den Born MV, Van Es JH, Clevers H

A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality

Cell
July 12, 2018

Daigle TL, Madisen L, Hage TA, Valley MT, Knoblich U, Larsen RS, Takeno MM, Huang L, Gu H, Larsen R, Mills M, Bosma-Moody A, Siverts LA, Walker M, Graybuck LT, Yao Z, Fong O, Nguyen TN, Garren E, Lenz GH, Chavarha M, Pendergraft J, Harrington J, Hirokawa KE, Harris JA, Nicovich PR, McGraw MJ, Ollerenshaw DR, Smith KA, Baker CA, Ting JT, Sunkin SM, Lecoq J, Lin MZ2, Boyden ES, Murphy GJ, da Costa NM, Waters J, Li L, Tasic B, Zeng H

A large-scale, standardized physiological survey reveals higher order coding throughout the mouse visual cortex

bioRxiv
June 29, 2018

de Vries S, Lecoq J, Buice MA, Groblewski PA, Ocker GK, Oliver M, Feng F, Cain N, Ledochowitsch P, Millman D, Roll K, Garrett M, Keenan T, Kuan L, Mihalas S, Olsen S, Thompson C, Wakeman W, Waters J, Williams D, Barber C, Berbesque N, Blanchard B, Bowles N, Caldejon S, Casal L, Cho A, Cross S, Dang C, Dolbeare T, Edwards M, Galbraith J, Gaudreault N, Griffin F, Hargrave P, Howard R, Huang L, Jewell S, Keller N, Knoblich U, Larkin J, Larsen R, Lau C, Lee E, Lee F, Leon A, Li L, Long F, Luviano J, Mace K, Nguyen T, Perkins J, Robertson M, Seid S, Shea-Brown E, Shi J, Sjoquist N, Slaughterbeck C, Sullivan D, Valenza R, White C, Williford A, Witten D, Zhuang J, Zeng H, Farrell C, Ng L, Bernard A, Phillips JW, R Reid C, Koch C

Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth in developing mice

PLOS | Biology
June 26, 2018

Roselló-Díez A , Madisen L, Bastide S, Zeng H, Joyner AL

The organization of intracortical connections by layer and cell class in the mouse brain

bioRxiv
April 18, 2018

Harris JA, Mihalas S, Hirokawa KE, Whitesell JD, Knox J, Bernard A, Bohn P, Caldejon S, Casal L, Cho A, Feng D, Gaudreault N, Gerfen C, Graddis N, Groblewski PA, Henry A, Ho A, Howard R, Kuan L, Lecoq J, Luviano J, McConoughey S, Mortrud M, Naeemi M, Ng L, Oh SW, Ouellette B, Sorensen SA, Wakeman W, Wang Q, Williford A, Phillips J, Jones A, Koch C, Zeng H

High resolution data-driven model of the mouse connectome

Network Neuroscience
April 1, 2018

Knox J, Harris KD, Graddis N, Whitesell JD, Zeng H, Harris JA, Shea-Brown E, Mihalas S

Nontoxic, double-deletion-mutant rabies viral vectors for retrograde targeting of projection neurons

Nature Neuroscience
March 5, 2018

Chatterjee S, Sullivan H, MacLennan BJ, Xu R, Hou Y, Lavin TK, Lea N, Michalski J, Babcock K, Dietrich S, Matthews GA, Beyeler A, Calhoon GG, Glober G, Whitesell J, Yao S, Cetin A, Harris J, Zeng H, Tye K, Reid RC, Wickersham IR

Systematic generation of biophysically detailed models for diverse cortical neuron types

Nature Communications
February 19, 2018

Gouwens NW, Berg J, Feng D, Sorensen SA, Zeng H, Hawrylycz MJ, Koch C, and Arkhipov A

Single-nucleus and single-cell transcriptomes compared in matched cortical cell types

PLoS One
December 26, 2018

Bakken TE, Hodge RD, Miller JA, Yao Z, Nguyen TN, Aevermann B, Barkan E, Bertagnolli D, Casper T, Dee N, Garren E, Goldy J, Graybuck LT, Kroll M, Lasken RS, Lathia K, Parry S, Rimorin C, Scheuermann RH, Schork NJ, Shehata SI, Tieu M, Phillips JW, Bernard A, Smith KA, Zeng H, Lein ES, Tasic B

Activation of neuromodulatory axon projections in primary visual cortex during periods of locomotion and pupil dilation

bioRxiv
December 19, 2018

Larsen RS, Turschak E, Daigle T, Zeng H, Zhuang J, Waters J

Distinct descending motor cortex pathways and their roles in movement

Nature
October 31, 2018

Economo MN, Viswanathan S, Tasic B, Bas E, Winnubst J, Menon V, Graybuck LT, Nguyen TN, Smith KA, Yao Z, Wang L, Gerfen CR, Chandrashekar J, Zeng H, Looger LL, Svoboda K

Shared and distinct transcriptomic cell types across neocortical areas

Nature
October 31, 2018

Tasic B, Yao Z, Graybuck LT, Smith KA, Nguyen TN, Bertagnolli D, Goldy J, Garren E, Economo MN, Viswanathan S, Penn O, Bakken T, Menon V, Miller J, Fong O, Hirokawa KE, Lathia K, Rimorin C, Tieu M, Larsen R, Casper T, Barkan E, Kroll M, Parry S, Shapovalova NV, Hirschstein D, Pendergraft J, Sullivan HA, Kim TK, Szafer A, Dee N, Groblewski P, Wickersham I, Cetin A, Harris JA, Levi BP, Sunkin SM, Madisen L, Daigle TL, Looger L, Bernard A, Phillips J, Lein E, Hawrylycz M, Svoboda K, Jones AR, Koch C, Zeng H

The Markov link method: a nonparametric approach to combine observations from multiple experiments

bioRxiv
October 30, 2018

Loper J, Bakken T, Sumbul U, Murphy G, Zeng H, Bleib D, Paninski L

Neuronal cell-type classification: challenges, opportunities and the path forward

Nature Reviews Neuroscience
September 2017

Zeng H, Sanes JR

The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas

Neuron
November 1, 2017

Ecker JR, Geschwind DH, Kriegstein AR, Ngai J, Osten P, Polioudakis D, Regev A, Sestan N, Wickersham IR, Zeng H

Adult mouse cortical cell taxonomy revealed by single cell transcriptomics

Nature Neuroscience
January 4, 2016

Tasic B, Menon V, Nguyen TN, Kim TK, Jarsky T, Yao Z, Levi B1, Gray LT, Sorensen SA, Dolbeare T, Bertagnolli D, Goldy J, Shapovalova N, Parry S, Lee C, Smith K, Bernard A, Madisen L, Sunkin SM, Hawrylycz M, Koch C, Zeng H

Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance

Neuron
March 4, 2015

Madisen L, Garner AR, Shimaoka D, Chuong AS, Klapoetke NC, Li L, van der Bourg A, Niino Y, Egolf L, Monetti C, Gu H, Mills M, Cheng A, Tasic B, Nguyen TN, Sunkin SM, Benucci A, Nagy A, Miyawaki A, Helmchen F, Empson RM, Knöpfel T, Boyden ES, Reid RC, Carandini M, Zeng H

A mesoscale connectome of the mouse brain

Nature
April 2, 2014

Oh SW, Harris JA, Ng L, Winslow B, Cain N, Mihalas S, Wang Q, Lau C, Kuan L, Henry AM, Mortrud MT, Ouellette B, Nguyen TN, Sorensen SA, Slaughterbeck CR, Wakeman W, Li Y, Feng D, Ho A, Nicholas E, Hirokawa KE, Bohn P, Joines KM, Peng H, Hawrylycz MJ, Phillips JW, Hohmann JG, Wohnoutka P, Gerfen CR, Koch C, Bernard A, Dang C, Jones AR, Zeng H

Genetic approaches to neural circuits in the mouse

Annual Review of Neuroscience
May 17, 2013

Huang JZ & Zeng H

Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures

Cell
April 13, 2012

Zeng H, Shen EH, Hohmann JG, Oh SW, Bernard A, Royall JJ, Glattfelder KJ, Sunkin SM, Morris JA, Guillozet-Bongaarts AL, Smith KA, Ebbert AJ, Swanson B, Kuan L, Page DT, Overly CC, Lein ES, Hawrylycz MJ, Hof PR, Hyde TM, Kleinman JE, Jones AR

A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing

Nature Neuroscience
March 25, 2012

Madisen L, Mao T, Koch H, Zhuo J, Berenyi A, Fujisawa S, Hsu YW, Garcia AJ, 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

A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

Nature Neuroscience
December 20, 2010

Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ, Jones AR, Lein ES, Zeng H