Research Overview

Our lab's mission is to understand the organizational principles that underlie information processing in neural circuits. We aim to discover the relationship between circuit structure and function in the Drosophila and rodent brain by applying and developing a technological platform sometimes called as '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. Serial EM provides us with detailed anatomical information about neurons and their connections. We can identify excitatory and inhibitory neurons and synapses, discover connectivity motifs, and analyze the organization 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 infer how patterns of connectivity shape 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 that will allow us to use behavior to bridge our understanding of circuit structure and network computation. By working across these modes of inquiry we aim to uncover the fundamental building blocks of functional networks.

About the Researcher

My expertise is in neuronal anatomy and physiology, large-scale electron microscopy (EM), in vivo multi-photon microscopy, and molecular genetics. I use these approaches to elucidate the logic and mechanisms specifying neural circuit connectivity.

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Researcher Areas

  • Structure function and development of neural circuits

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PUBLICATIONS

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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Lee WC, Reid RC. Specificity and randomness: structure-function relationships in neural circuits. Curr Opin Neurobiol. 2011 Oct; 21(5):801-7. View abstract
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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