​1.Functional myelin: physiological, pathological and developmental significance

​The human central nervous system (CNS) consists of two different types of axons, myelinated and unmyelinated, which propagate nerve pulses for neural communication. Axonal myelin plays a significant role in sustaining normal information coding and propagation. Axonal myelination constitutes an important step in neural development and neural network formation. Myelin impairment and degree of demyelination has been monitored using diffusion tensor imaging (DTI), as a read-out of pathophysiology for neurological diseases such as spinal cord injury, stroke, and cerebral palsy. A detailed comparison between the physiological functions of myelinated and unmyelinated axons, as well as their different behaviors under pathological conditions (i.e. brain ischemia), and during development, have not been fully performed. (Figure: compound action recording from corpus callosum).

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​​2.Electric guidance of adult neuronal precursor stem cells (aNPC)

The adult human brain provides a very limited capability of neuronal regeneration. Only a small portion of the newly generated adult stem cells (aNPCs) can migrate to the damaged brain area. Direct transplantation of the harvested, cultured stem cells into the injured area is the future of cell therapy. Unfortunately, the transplanted cells have a great difficulty migrating themselves inside the injured tissue and integrating within the existing cells. In this project, we will combine biophysics modeling, stem cell biology, pharmacology and whole cell patching to investigate the mechanisms underlying stem cell migration and differentiation in the electric field. (Figure: Stem cell culture, immune staining and whole cell recording).

 

​3.Biophysics simulation on cellular bio-mechanics under electric and magnetic stimulation

Cells deform and migrate under electric field, partially mediated by the interactions between the field and the electric charges on the cell membrane. Two kinds of charges present on the cell membrane: the intrinsic charges carried by the charged proteins, and the free charges induced by the electric field. How do these surface charges involve in the bio-mechanics of the cells that contribute to the membrane deformation and migration of the cell? (Figure: surface charge distribution on a model cell and force generated on cell membrane).

 

4. Deficit in synaptic transmission in Alzheimer’s neurons – a mechanistic study with whole cell patching

Neurons communicate via synaptic transmission of chemicals across the synaptic cleft, the gap that separates the two neurons. In Alzheimer’s disease (AD), this communication is impaired, which may be responsible for the damaged cognitive and emotional function observed in AD patients. The neuro-pathological mechanism of such impairment is not completely clear, which hinders the development of effective medical treatments to rescue this pathological deficit. Although it is postulated that the aggregation and plaque formation of Beta-Amyloid is responsible for many of the neurological impairments seen in AD, previous studies have also suggested that synaptic dysfunction and memory impairment can occur at an earlier AD stage, when only soluble A-beta presents. Electrophysiological studies of transgenic young mice have revealed a significant deficit in basal synaptic transmission before plaque formation and neuronal loss. These studies suggest that there are functional changes in early AD, prior to the occurrence of accumulated amyloid plaques, which warrant further investigations into mechanisms of early AD pathology. This project is specifically designed to answer the question: is the communication deficit in early AD between two neurons caused by pathological changes in the signal sending (presynaptic) neuron, or the signal receiving (postsynaptic) neuron, or both? (Figure: Whole cell recording from a hippocampal cell, showing trains of action potential during current clamp and pharmacological blockage of spontaneous synaptic activity).

 

 

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