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Neurology Research
F.M. Kirby Neurobiology Center

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.

Research Background

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.

 

Publications

  1. Synaptic wiring motifs in posterior parietal cortex support decision-making. Nature. 2024 Mar; 627(8003):367-373. View Abstract
  2. Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch. Neuron. 2023 10 18; 111(20):3211-3229.e9. View Abstract
  3. The projection-specific signals that establish functionally segregated dopaminergic synapses. Cell. 2023 08 31; 186(18):3845-3861.e24. View Abstract
  4. Biomechanical origins of proprioceptor feature selectivity and topographic maps in the Drosophila leg. Neuron. 2023 10 18; 111(20):3230-3243.e14. View Abstract
  5. Local shape descriptors for neuron segmentation. Nat Methods. 2023 02; 20(2):295-303. View Abstract
  6. Structured cerebellar connectivity supports resilient pattern separation. Nature. 2023 01; 613(7944):543-549. View Abstract
  7. Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties. Nat Neurosci. 2022 06; 25(6):702-713. View Abstract
  8. Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical synapse development. Cell Rep. 2022 02 22; 38(8):110416. View Abstract
  9. Automatic detection of synaptic partners in a whole-brain Drosophila?electron microscopy data set. Nat Methods. 2021 07; 18(7):771-774. View Abstract
  10. Reconstruction of motor control circuits in adult Drosophila using automated transmission electron microscopy. Cell. 2021 02 04; 184(3):759-774.e18. View Abstract
  11. Dense neuronal reconstruction through X-ray holographic nano-tomography. Nat Neurosci. 2020 12; 23(12):1637-1643. View Abstract
  12. Sensory Experience Engages Microglia to Shape Neural Connectivity through a Non-Phagocytic Mechanism. Neuron. 2020 11 11; 108(3):451-468.e9. View Abstract
  13. Multiplexed peroxidase-based electron microscopy labeling enables simultaneous visualization of multiple cell types. Nat Neurosci. 2019 05; 22(5):828-839. View Abstract
  14. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Rep. 2018 07 24; 24(4):973-986.e8. View Abstract
  15. Wiring variations that enable and constrain neural computation in a sensory microcircuit. Elife. 2017 05 22; 6. View Abstract
  16. Whole-brain serial-section electron microscopy in larval zebrafish. Nature. 2017 05 18; 545(7654):345-349. View Abstract
  17. Anatomy and function of an excitatory network in the visual cortex. Nature. 2016 Apr 21; 532(7599):370-4. View Abstract
  18. Large-scale automated histology in the pursuit of connectomes. J Neurosci. 2011 Nov 09; 31(45):16125-38. View Abstract
  19. Inhibitory dendrite dynamics as a general feature of the adult cortical microcircuit. J Neurosci. 2011 Aug 31; 31(35):12437-43. View Abstract
  20. Specificity and randomness: structure-function relationships in neural circuits. Curr Opin Neurobiol. 2011 Oct; 21(5):801-7. View Abstract
  21. Network anatomy and in vivo physiology of visual cortical neurons. Nature. 2011 Mar 10; 471(7337):177-82. View Abstract
  22. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protoc. 2009; 4(8):1128-44. View Abstract
  23. 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
  24. Multifocal multiphoton microscopy based on multianode photomultiplier tubes. Opt Express. 2007 Sep 03; 15(18):11658-78. View Abstract
  25. Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex. PLoS Biol. 2006 Feb; 4(2):e29. View Abstract
  26. Regulation of cpg15 by signaling pathways that mediate synaptic plasticity. Mol Cell Neurosci. 2003 Nov; 24(3):538-54. View Abstract
  27. 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

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