To understand how the brain wires, integrates sensory cues and generates motion commands is a major challenge in Neuroscience. The zebrafish and Xenopus tadpole, genetically accessible vertebrates with transparent embryos, represent excellent in vivo animal models for understanding the development, function and disease of the nervous system. Using genetic manipulations, in vivo patch clamp recording, in vivo imaging and behavior assays, we plan to study the following questions.
Development of the visual system
Elaboration of the dendritic arbors and formation of appropriate synaptic connections are essential to the development of neural circuits. Initially, they largely depend on gene-based intrinsic developmental programs. At later development stages, it is suggested that they critically depend on epigenetic factors, such as spontaneous activity. The retina is a natural brain slice with a laminar structure. In the mature retina, dendrites of retinal ganglion cells (RGCs) in the inner plexiform layer (IPL) are separated into ON and/or OFF sublamina. At early developmental stages, however, the dendrites of most RGCs are diffusedly ramified throughout the IPL. Thus, RGCs can serve as an ideal model to examine mechanisms underlying refinements of dendritic arbors and synaptic connectivity during development. Using in vivo recording and imaging, we will address what factors (such as visual experience, spontaneous activity, glial cell activity, GABAergic inputs, retrograde factors) affect the development of functional (including intrinsic membrane properties, ON-/OFF-pathway specific excitatory and inhibitory synapses) and morphological (sublaminar arborization of dendrites) properties of RGCs and the mechanisms through which this is achieved. In addition, we will study the plasticity of ribbon synapses made by retinal bipolar cells on RGC dendrites.
Multimodal sensory integration and behavior
Animals dynamically integrate multimodal sensory cues and generate adapted behaviors to environmental changes. However, the underlying neural mechanism remains unknown. The optic tectum of the zebrafish integrates multimodal sensory inputs and translates them into pre-commands, which are sent to the hindbrain (such as Mauthner cells) and subsequently to the spinal cord to initiate behavior. Using in vivo recording/imaging of retinal ganglion cells, tectal neurons, Mauthner cells and motoneurons, we will first study neural mechanisms underlying multimodal sensory integration and behavior generation. Furthermore, in combination with behavior assays, we will address how sensory integration and its plasticity are involved in learning and memory-based behaviors, such as avoidance behavior.
Neural regulation of vasculature system
The functional integrity of the brain critically relies on a delicate balance between substrate delivery via blood flow and energy demands imposed by neural activity. Neurons, astrocytes and vascular cells constitute a functional unit, the neurovascular unit, to ensure that active brain areas obtain an adequate amount of blood. However, it is poorly understood how neural activity locally regulates brain microcirculation. The blood vessels in the optic tectum of the zebrafish can be readily imaged in vivo. Using in vivo recording/imaging of neuronal activity, glial activity and blood flow, we will study how sensory inputs and neural activities regulate the development and function of the vasculature system. Furthermore, we will explore how neural activities regulate the permeability of blood-brain barrier (BBB) under physiological and pathological conditions, such as neurodegenerative diseases.