Brain Star Award winner Hovy Ho-Wai Wong

A role for axonal protein synthesis in information coding in the brain

Neurons are specialized cells that transmit signals by transforming inputs received into an electric impulse. This impulse travels through a structure called the axon that can extend far from the cell body to reach another cell. The synapse is a space between neurons into which transmitting neurons, called pre-synaptic neurons, release neurotransmitters that are sensed by the receiving, post-synaptic, neurons. Modulation of the strength of synapses is important for information transfer and memory formation. But with synapses typically located far away in axons, it has been unclear how proteins are delivered from the cell body to the right place and at the right time to support local functions.

Previous studies have shown that local production of proteins specifically in the post-synaptic end of a neuron is important for making a synapse stronger or weaker. However, little was known about the mechanisms at play in the pre-synaptic neuron. Contradictory results existed in the literature about the role of protein synthesis in axons in modulating the strength of synapses, some reporting it was important and others that it was not. Through an elegant series of experiments, Hovy Wong and colleagues at McGill University have elucidated the functional role of local protein synthesis in axons, the mechanism by which this occurs, and its role in transmission of specific signals.

Hovy Wong and colleagues showed that protein synthesis in axons regulates high- but not low-frequency transmission. As high-frequency transmission is associated with high-fidelity information transfer and memory formation, these results change how we think about the role of protein synthesis in learning and memory. The researchers furthermore revealed that axonal protein synthesis sustains excitatory neurotransmission onto excitatory but not inhibitory neurons. This paints a picture that, based on target cell type, synapses from the same axon are differentially regulated by axonal protein synthesis, and elegantly explains many of the contradictions previously reported in the literature. Imbalances between excitatory and inhibitory signals are associated with many neuropathologies like autism and epilepsy, so this work opens new doors to disease research. The findings also reveal previously unexplored therapeutic potential.

About Dr. Hovy Ho-Wai Wong

Dr. Hovy Ho-Wai Wong performed this research as a post-doctoral fellow in the laboratory of Dr. Jesper Sjöström at McGill University. Under Dr. Sjöström supervision, Hovy realized his research program on protein synthesis in neurotransmission, which was inspired by the work he performed during his PhD training in the laboratory of Dr. Christine Holt, at the University of Cambridge. Hovy is excited that after decades of debate, the work he performed as a PhD student and later as a postdoctoral fellow has changed the way the field thinks about the existence of axonal protein synthesis by showing its role in intact circuits.

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Sources of funding

• Canadian Institutes for Health Research (CIHR)
• Canada First Research Excellence Fund (CFREF)
• McGill Healthy Brains Healthy Lives Initiative (HBHL)
• Fonds de recherche du Québec – Santé (FRQS)
• Quebec Bio-imaging Network (QBIN)
• Natural Sciences and Engineering Research Council of Canada (NSERC)
• Canadian Foundation for Innovation (CFI)