Overview

Understanding How the Brain Wires Itself

Our lab focuses on the regulation of central nervous circuit construction and behavioral output. We combine molecular, cellular, and systems-level approaches — exploiting the unique optical and genetic accessibility of the Xenopus laevis tadpole to connect gene expression events to circuit architecture and animal behavior.

Research Area 01 · Neurogenesis

Neural Progenitor Proliferation & Differentiation

Neurogenesis · Epigenetics

We study the molecular logic governing radial glial cell proliferation and the differentiation of neurons destined for specific positions within visual circuits. A central interest is how histone deacetylases and Wnt signaling encode cell fate decisions in response to sensory experience.

How do radial glial cells decide to self-renew versus differentiate?
What signals determine the laminar identity of newborn neurons?
How do newly born neurons integrate into pre-existing circuits?
Which nascent proteins, induced by visual activity, drive structural plasticity?
Key findings: HDAC1- and HDAC3-dependent regulation of radial glial proliferation in response to visual experience; β-Catenin/SOX2 interaction in neural stem cell homeostasis in the developing Xenopus thalamus.
Radial GliaHDAC1 / HDAC3Wnt / β-CateninSOX2Nascent ProteomeOptic Tectum
Research Area 02 · E/I Balance

Excitation–Inhibition Balance & Neurological Disease

Circuit Function · Disorders

The dynamic balance between glutamatergic excitation and GABAergic inhibition governs every aspect of circuit function. Its disruption is a common thread in autism spectrum disorder, epilepsy, and schizophrenia. We dissect the molecular machinery of E/I homeostasis and its behavioral consequences.

How does E/I balance regulate structural and functional circuit plasticity?
How do inhibitory interneurons adapt to changing excitatory drive?
What molecules mediate E/I homeostasis at single-cell resolution?
Can restoring E/I balance correct circuit dysfunction and behavior?
Key findings: Nature Communications study demonstrating cell-autonomous regulation of inhibitory neuron plasticity by excitatory inputs; GABA-A receptor-dependent transmission sculpts dendritic arbor structure in vivo.
E/I BalanceInterneuronsGABA-A ReceptorsEpilepsyAutismIn Vivo Recording
Research Area 03 · Plasticity

Experience-Dependent Synaptic Plasticity

Homeostasis · AMPAR Trafficking

Visual experience drives profound structural and functional remodeling during the critical period. We investigate how activity is translated into lasting changes in synaptic strength through epigenetic regulation, receptor trafficking, and local protein synthesis — and how homeostatic mechanisms preserve circuit stability.

How does visual experience regulate nascent protein synthesis at synapses?
What epigenetic marks encode long-lasting plasticity?
How does Rab5c-mediated AMPAR endocytosis scale down synapses?
What is CPEB's role in acute behavioral plasticity?
Key findings: Prolonged visual experience accelerates synaptic downscaling through epigenetic modification and Rab5c-mediated AMPAR endocytosis (Commun Biol 2026); acute CPEB synthesis required for visual avoidance plasticity (Cell Rep 2014).
AMPA ReceptorsRab5cSynaptic ScalingCPEBEpigeneticsCritical Period
Research Area 04 · Neurotoxicology

Environmental Neurotoxicity & Neuroprotection

Toxicology · Translational

Environmental pollutants disrupt developing nervous systems. We use Xenopus as a high-throughput in vivo platform to characterize how industrial chemicals such as para-xylene impair neural development, and to identify small molecules that restore neuronal health.

How does para-xylene induce neural apoptosis and behavioral deficits?
What epigenetic mechanisms underlie chemically induced neurotoxicity?
Can D-Glucuronolactone protect the developing CNS from oxidative damage?
How can Xenopus serve as a translational toxicology screening model?
Key findings: D-Glucuronolactone attenuates para-xylene-induced neuronal deficits; oxidative stress is the primary driver of para-xylene CNS toxicity; Xenopus validated as a powerful and ethically efficient toxicological model.
Para-xyleneOxidative StressD-GlucuronolactoneApoptosisBTEXDevelopmental Toxicology
Methods & Tools

Key Techniques

01 /

In Vivo Electrophysiology

Whole-cell patch-clamp and field recordings in intact Xenopus tadpoles to measure synaptic currents, E/I ratios, and circuit activity in the optic tectum in real time.

02 /

Two-Photon Imaging

Live imaging of fluorescently labeled neurons over days in the same animal, tracking dendritic arbor dynamics, axonal branching, and synapse formation.

03 /

Genetic Manipulation

In vivo electroporation, morpholino knockdown, and CRISPR/Cas9 for precise gain- and loss-of-function studies in the intact developing brain.

04 /

Single-Cell Transcriptomics

scRNA-seq to characterize cell type diversity and transcriptional states, enabling whole-brain cell atlas construction across Xenopus development.

05 /

Proteomics & Biochemistry

Mass spectrometry-based nascent proteomics, co-IP, and western blotting to identify molecular players in visual experience-dependent plasticity.

06 /

Behavioral Assays

Quantitative visual avoidance, optomotor response, and phototaxis assays linking molecular and circuit changes to meaningful behavioral readouts.

Collaborations

Key Collaborators

Hollis T. Cline
The Scripps Research Institute, USA
Chinese Institute for Brain Research, China
Guoji Guo
Zhejiang University, China
Mengsheng Qiu
Hangzhou Normal University, China
Junqiu Liu
Hangzhou Normal University, China
Dingcheng Zhu
Hangzhou Normal University, China
Xiaoping Han
Zhejiang University, China
Georgetown University, USA