In vivo imaging of a living brain is essential in the understanding of the interactions between the tens of billions of neurons, the specialised cells that form the foundation of the brain’s many functions, and the synapses that allow transmission of information between neurons.
This requires technologies with high spatial and temporal resolution to truly understand the dynamics at work. However, the different forms of imaging technology currently available to scientists have their respective limitations, including the unsuitableness for the live imaging of biological tissues, limiting synaptic resolution and imaging depth.
Now a collaboration between a neuroscientist Professor Nancy Ip (Croucher Senior Research Fellowship 1998) and an engineering faculty Professor Jianan Qu, both at Hong Kong University of Science and Technology (HKUST), has led to the successful development of a new imaging technology – adaptive optics two-photon endomicroscopy. This enables in vivo imaging of deep brain structures at high resolution, shedding light on brain functions in regions that have never been well explored.
Adaptive optics technology was originally developed for ground-based telescopes that carry out astronomical research. The technology employs a bright star, or a so-called “guide star”, to measure light distortion of the atmosphere and then compensates for the distortion using a deformable mirror.
In developing the adaptive optics two-photon endomicroscopy system, the HKUST research group similarly used a localised fluorescence signal as the “guide star” inside biological tissues, which allowed them to measure the aberration of the miniature endoscope employed with reference to the brain tissue.
Using the new technology, the scientists investigated neuronal plasticity in the hippocampus, a critical deep brain structure with a major role in memory and learning, and revealed the relationship between the somatic and dendritic activities of pyramidal neurons within the hippocampus. Their findings were published in Science Advances.
Among Ip’s internationally renowned research endeavours, she is seeking to understand the impairment of neuronal communication at the hippocampus in Alzheimer’s disease and is especially interested in developing ways to improve neuronal communication in this area of the brain.
“The development of the two-photon endomicroscopy system is significant. We can now examine the dynamic changes of structural synapses in the hippocampus,” Ip said.
“Meanwhile, we are also able to examine the firing activities of different populations of neurons in the hippocampus. This will facilitate our understanding of the molecular basis of learning and memory and its deregulation in memory dysfunctions in many neurological diseases.”
Nancy Y Ip is The Morningside Professor of Life Science in the Division of Life Science, and Director of the State Key Laboratory of Molecular Neuroscience at The Hong Kong University of Science and Technology (HKUST). She received her PhD in Pharmacology from Harvard University, US, and went on to work as a Senior Staff Scientist at Regeneron Pharmaceuticals Inc, New York. Since joining HKUST in 1993, she has served as Associate Dean of Science (1998-2005), Director of the Biotechnology Research Institute (1996-2008), Head of the Department of Biochemistry (2000-2009) , Dean of Science (2011-2016) and Vice-President for Research and Development (2016-2022). She received her Croucher Senior Research Fellowship in 1998.
- Ip’s personal profile (The Croucher Foundation): https://scholars.croucher.org.hk/scholars/nancy-ip-yuk-yu
- Ip’s personal profile (The Hong Kong University of Science and Technology): https://life-sci.hkust.edu.hk/team/nancy-yuk-yu-ip/
- The scientific paper Prof. Ip published in Science Advances in 2020: https://www.science.org/doi/10.1126/sciadv.abc6521