Unravelling Mysteries of The Brain in Health & Disease
Focus
Brain circuit formation, maintenance, and plasticity, with a strong emphasis on understanding the molecular signalling at connections, known as synapses.
Why?
Synapses are vital for information processing and memory storage, yet we have surprisingly limited understanding of their functioning principles. Synapses are also dysregulation hotspots in neurological disorders and may present viable drug targets.
What's new?
A synapse has a presynaptic transmitting end and a postsynaptic receiving end. While the postsynapse has been intensely studied, knowledge of the presynapse lags behind. Our work bridges the gap by taking on a combined pre- and postsynaptic focus on neural circuits in health and disease.
How?
We employ multidisciplinary techniques that link multiple levels of neurobiology, including 1) molecular regulation, 2) cellular changes, and 3) functional significances. To name a few, quadruple patch-clamp recordings (electrophysiology), custom 2-photon laser scanning microscopy, optogenetics, molecular biology, multi-omics bioinformatics. We are also keen on developing new labelling and live-imaging technologies, e.g. for RNA and protein synthesis, to uncover spatiotemporal dynamics in compartmentalized signalling.
Molecular Regulation
Cellular Changes
Functional Significance
Long-term goals
To uncover fundamental principles of neural circuits.
And to leverage this knowledge to reveal pre- and postsynaptic targets for alleviating neuropathologies.
Gallery
Quad-patch of layer-5 cortical neurons: The stars who made it to the cover of Nature Protocols 20(8)
Retinal ganglion cell axon in vivo: Navigating through the optic tract and arborizing after reaching the optic tectum. Axon was labelled by mRFP (red) and expressed GFP-tagged microtubule plus-end tracking protein EB1 (green).
The first quad after COVID restriction: After months of lockdown of the Montreal General Hospital, this is the first quad that Hovy got and has great sentimental value.
Local protein synthesis in vivo: The retinal axon was labelled by mRFP (purple). Cy5-RNA (white) was imaged at the same time as local mRNA translation of β-actin. Newly synthesized β-actin is shown as a heatmap after fluorescence recovery after photobleaching (FRAP).
RNA localization & synapse formation
Trying or Neuron cover 2017 A [failed]: Axon branching occurs far away from the cell body. Wong et al. (pages xxx-xxx) demonstrate that local protein synthesis serves as an important mechanism for promoting this decentralized process. The cover art shows a retinal axon arborizing in the optic tectum. Docked RNA granules (red) set up microdomains rich in nascent proteins (pink and white dots) promoting the emergence and stabilization of axonal branches. Artwork by William A. Harris.
Trying for Neuron cover 2024 [failed]: An unedited raw film photograph taken by Hovy Wong in The Camera Obscura & World of Illusions, Edinburgh, UK. The photo captured an approximately three-meter-wide tunnel with a green lens flare at the bottom left. In a different view, this photo could illustrate a narrow axon viewed from inside the cell body, and the lens flare a protein intended for delivery to a synapse. On this scale, you would need to transport each protein the equivalent of kilometers down the tunnel to reach the targets at the nerve endings. In this issue of Neuron, Wong et al. (pages xxx–xxx) reveal how proteins synthesized locally at the distal nerve endings support neurotransmitter release. Therefore, not all presynaptic proteins journey from soma to synapse.
Trying for Neuron cover 2017 B [failed]: Artwork by William A. Harris.
A quad that is often associated with Star Wars by many
Trying for Neuron cover 2017 C [failed]: Artwork by William A. Harris.
2-photon laser axotomy Using 2-photon laser to perform a micron-precise cut to separate the axon from the cell body.
Protein synthesis in cortical neurons: Puromycin labelling was used as mRNA translation proxy. The colours code for different deepths in the brain tissue.
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