Research Overview

Our lab's mission is to understand the organizational principles that underlie information processing in neuronal circuits. We aim to discover how network function and behavior arise from circuit wiring in the rodent and Drosophila brain. To do so, we develop and apply technologies called 'functional connectomics'.

Our work is guided by several key questions:

  • What rules underlie network connectivity?
  • What network motifs are conserved and what differentiates brains - and brain regions?
  • What are fundamental constraints on network behavior?
  • How are such rules enforced during development?

We primarily use large-scale electron microscopy (EM) and in vivo multi-photon calcium imaging to examine the structure and function of neurons and networks. Volumetric EM provides detailed structural information about cells and their connections. We can identify excitatory and inhibitory neurons and synapses, discover connectivity motifs, and analyze the nature of synaptic connections. The other key component of our approach is physiology – either optical imaging of activity sensors or electrophysiology. Ideally, the same cells are subjected to in vivo physiological recording and connectivity analysis. In this way we can unravel how wiring patterns enable neuronal computations.

Additionally, we use genetic tools for labeling and manipulation; and modeling to explore the implications of our data and generate testable theories. Finally, we are devising approaches to bridge analysis of behavior with circuit structure and network computation. By working across these modes of inquiry our goal is to uncover the fundamental building blocks of functional networks.

About Wei-Chung Allen Lee

Wei-Chung Allen Lee did his graduate work with Elly Nedivi at MIT studying neuronal structural plasticity. He did his postdoctoral work with Clay Reid at Harvard Medical School studying neural connectivity and coding in the visual cortex. Wei’s lab started in the fall of 2016 when he joined the faculty of the F.M. Kirby Neurobiology Center at Children's Hospital. He was the recipient of a Ruth Kirchstein NIH NRSA postdoctoral fellowship from the National Eye Institute and his current work is supported by the NIH BRAIN Initiative.

Researcher Services

Researcher Areas

  • Structure function and development of neural circuits

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PUBLICATIONS

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  1. Coulter ME, Dorobantu CM, Lodewijk GA, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ, Gaudin R, Walsh CA. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Rep. 2018 Jul 24; 24(4):973-986.e8. View abstract
  2. Tobin WF, Wilson RI, Lee WA. Wiring variations that enable and constrain neural computation in a sensory microcircuit. Elife. 2017 05 22; 6. View abstract
  3. Hildebrand DGC, Cicconet M, Torres RM, Choi W, Quan TM, Moon J, Wetzel AW, Scott Champion A, Graham BJ, Randlett O, Plummer GS, Portugues R, Bianco IH, Saalfeld S, Baden AD, Lillaney K, Burns R, Vogelstein JT, Schier AF, Lee WA, Jeong WK, Lichtman JW, Engert F. Whole-brain serial-section electron microscopy in larval zebrafish. Nature. 2017 05 18; 545(7654):345-349. View abstract
  4. Lee WC, Bonin V, Reed M, Graham BJ, Hood G, Glattfelder K, Reid RC. Anatomy and function of an excitatory network in the visual cortex. Nature. 2016 Apr 21; 532(7599):370-4. View abstract
  5. Kleinfeld D, Bharioke A, Blinder P, Bock DD, Briggman KL, Chklovskii DB, Denk W, Helmstaedter M, Kaufhold JP, Lee WC, Meyer HS, Micheva KD, Oberlaender M, Prohaska S, Reid RC, Smith SJ, Takemura S, Tsai PS, Sakmann B. Large-scale automated histology in the pursuit of connectomes. J Neurosci. 2011 Nov 09; 31(45):16125-38. View abstract
  6. Chen JL, Flanders GH, Lee WC, Lin WC, Nedivi E. Inhibitory dendrite dynamics as a general feature of the adult cortical microcircuit. J Neurosci. 2011 Aug 31; 31(35):12437-43. View abstract
  7. Lee WC, Reid RC. Specificity and randomness: structure-function relationships in neural circuits. Curr Opin Neurobiol. 2011 Oct; 21(5):801-7. View abstract
  8. Bock DD, Lee WC, Kerlin AM, Andermann ML, Hood G, Wetzel AW, Yurgenson S, Soucy ER, Kim HS, Reid RC. Network anatomy and in vivo physiology of visual cortical neurons. Nature. 2011 Mar 10; 471(7337):177-82. View abstract
  9. Holtmaat A, Bonhoeffer T, Chow DK, Chuckowree J, De Paola V, Hofer SB, Hübener M, Keck T, Knott G, Lee WC, Mostany R, Mrsic-Flogel TD, Nedivi E, Portera-Cailliau C, Svoboda K, Trachtenberg JT, Wilbrecht L. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protoc. 2009; 4(8):1128-44. View abstract
  10. Lee WC, Chen JL, Huang H, Leslie JH, Amitai Y, So PT, Nedivi E. A dynamic zone defines interneuron remodeling in the adult neocortex. Proc Natl Acad Sci U S A. 2008 Dec 16; 105(50):19968-73. View abstract
  11. Kim KH, Buehler C, Bahlmann K, Ragan T, Lee WC, Nedivi E, Heffer EL, Fantini S, So PT. Multifocal multiphoton microscopy based on multianode photomultiplier tubes. Opt Express. 2007 Sep 03; 15(18):11658-78. View abstract
  12. Lee WC, Huang H, Feng G, Sanes JR, Brown EN, So PT, Nedivi E. Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex. PLoS Biol. 2006 Feb; 4(2):e29. View abstract
  13. Fujino T, Lee WC, Nedivi E. Regulation of cpg15 by signaling pathways that mediate synaptic plasticity. Mol Cell Neurosci. 2003 Nov; 24(3):538-54. View abstract
  14. Lee WC, Nedivi E. Extended plasticity of visual cortex in dark-reared animals may result from prolonged expression of cpg15-like genes. J Neurosci. 2002 Mar 01; 22(5):1807-15. View abstract