C. elegans is a compact model to study the fundamental principles that govern circuit assembly, remodeling, and function, at the molecular, cellular and systems level.
We combine electron microscopy, genetics, optogenetics, calcium imaging, and electrophysiology to address how the neural circuit develops and operates at the molecular and system level.
We apply tools built and insights obtained from these studies to establish C. elegans models to reveal circuit deficits underlying human neurological disorders.
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1) Developmental connectomics. We lack understanding on the general impact of postnatal development on circuit infrastructure maturation and behavioral adaptation. The numerical simplicity of the C. elegans nervous system allows us to address this question at the systems level. We have established a cutting edge EM platform to reconstruct and identified precise wiring differences of the entire nervous system across development.
2) Neural coding of behaviors. We seek principles that translate neural connectivities to behaviors. Combining genetics, calcuim imaging and electrophysiology, we are identifying the function of each neuron and their connections to the animal's behavioral output, including the identity and regulation of intrinsic oscillators (CPGs).
3) Mechanisms that establish anatomic and functional connections. Applying the structural and functional analysis pipelines to C. elegans mutants, we are defining molecular pathways that determine the wiring specificity and functionality during development.
4) Neuronal excitability and CLIFADD. We have identified key components of neuronal excitability, the sodium and potassium leak channels. We revealed the first case of a human patient of CLIFADD, a developmental disorder caused by gain-of- function mutations in the Na leak channel. We are assessing the circuit-level effect of these pathological mutations and seek potential treatment for this disorder.