Research Interests

RESEARCH INTERESTS

    Brain cells communicate with each other through specialized contact sites called synapses. Neuronal outgrowth patterns and synapse formation (synaptogenesis) are established during the early stage of development and throughout life. They form the basis for all animal behaviors, ranging from simple reflexes to complex cognitive functions such as learning and memory. Extrinsic factors, such as trophic factors present in the extracellular milieu, are deemed important for the appropriate development of brain connectivity. Similarly, environmental toxins (e.g. heavy metals) and various anti-psychiatric medications (Prozac etc.) have been shown to negatively impact brain cell connectivity, indicating their potential involvement in developmental (e.g. autism spectrum) or neurodegenerative (e.g. Alzheimer’s Diseases) disorders. It is therefore important for us to understand the effects of these factors (positive versus negative) and their underlying mechanisms (cellular pathways, targeted genes or proteins etc).

                                                                            Fig. 1: Lymnaea Stagnalis as a Research Model

    To gain an in-depth understanding of the effects of environmental factors on neurite outgrowth and synaptogenesis, our laboratory utilizes the soma-soma synapse model derived from the fresh pond snail, Lymnaea stagnalis (Fig. 1A). In this model, synaptogenesis can be investigated at single pre- and post-synaptic neurons (Fig. F). Lymnaea brain is comprised of about 11 ganglia (Fig. B), which contain around 20-30,000 neurons in total. When single neurons are cultured in vitro in the presence of growth factors, not only do they regenerate their functional processes (e.g. growth cones and neuritis, Fig. D&E), but they also recapitulate synaptic connectivity patterns that resemble the ones formed in vivo. The large size of the cell body, the ease of cell culture and the robust regenerative capability make Lymnaea a powerful model for studying neurobiological mechanisms of animal development and behaviors in single cell levels. In addition, these neurons are highly accessible for state-of-the-art electrophysiology, neuro-chip bionic interface, calcium imaging, amperometry, immunocytochemistry, and molecular biological techniques.

Using these techniques, our laboratory also investigates how trophic factors or neurotoxins impact genes, proteins, intracellular organelles, and signaling pathways during large neuronal network assembly and function in the early stage of brain development. Specifically, we use primary cell cultures of rat cortical or hippocampal neurons (Fig. 2) and examine the effects of trophic factors or neurotoxins on the development of neuritic processes, cytoskeletal components, synaptic proteins, and synaptic currents during the assembly of a large scale of the network.

                                                            Fig. 2 Rat Neuronal Cell Culture and Modern Neuroscience Recordings