PiN Faculty Member - Wei-Chung Allen Lee, PhD

Wei-Chung Allen Lee, PhD

F.M. Kirby Neurobiology Center, Boston Children's Hospital

Harvard Medical School
Goldenson Building Room 243
220 Longwood Avenue
Boston, MA 02115
Tel: 617-432-1326
Email: wei-chung_lee@hms.harvard.edu
Visit my lab page here.



Our goal is to understand the organizational principles that underlie information processing in neural circuits.

We apply and develop 'functional connectomics' as a platform to discover the relationship between circuit structure and function in the Drosophila and rodent brain.

An advantage of studying neuronal circuits in the fly is that whole brain regions, and even whole brains, can be captured in serial electron microscopy (EM) datasets. Many Drosophila neurons are uniquely identifiable, genetically accessible, and there is an increasing wealth of information about the physiology of these identified neurons. Furthermore, these cells often show a remarkable degree of physiological stereotypy. Because an entire network often only contains hundreds of cells, it is possible to completely reconstruct functional networks. We can leverage these facts to correlate connectivity and function, and expect to learn general principles in the fly that are conserved in larger networks.

The mouse behavioral repertoire is richer and more flexible than that of the fly. And the mouse brain may be more comparable to the human brain in both health and disease. The cortex is key to many of the complex behaviors that distinguish mammals from flies, but the organizational principles that support this complexity are not well understood.

Our work is focused on a few key questions:

--What rules determine network connectivity? How are these rules enforced during development?
--How do local networks process information and how does this relate to long-range processing?
--What network motifs are conserved and what differentiates brains and brain regions?
--What are the fundamental constraints on network behavior?

We primarily use large-scale EM and in vivo multi-photon calcium imaging to examine the structure and function of neurons and networks. Serial section 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.



Last Update: 3/28/2017



Publications

For a complete listing of publications click here.

 


 



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