A new study from RI-MUHC researchers finds that synaptic connections in the brain can produce their own proteins in response to periods of high demand

In a new study recently published in the journal Neuron, RI-MUHC researchers have clarified the mechanism by which neurons create and make use of the protein building blocks they need to communicate with one another in the brain.

Led by Per Jesper Sjöström, scientists from the Brain Repair and Integrative Neuroscience Program (BRaIN) at the Research Institute of the McGill University Health Centre (RI-MUHC) and McGill University have revealed a new way in which neurons sustain high-intensity neurotransmitter release. The team found that some proteins are made locally on demand.

Acquisition with 2-photon laser scanning microscopy after performing quadruple whole-cell electrophysiological recording for neurotransmission. Cells in different colours were selectively loaded with either protein synthesis inhibitor or control solution. In this image, cells in red were loaded with an inhibitor of protein synthesis initiation. Cells in cyan were loaded with control internal solution. (Credit: Hovy Wong)

An axon is a neuronal output fiber that conveys information to the other cells via synaptic connections. These fibers were thought to be passive conduits, much like electrical cables.

“In the textbook view, proteins are made in the cell body and then transported to where they are needed,” says Professor Sjöström. “However, neurons connect to other neurons with processes that can be centimetres long. When these processes can be so long, and so far from the cell body, how do neurons deliver proteins to the right place and at the right time? This is the question we set out to answer.”

The researchers found that proteins are locally made in axons to boost neurotransmitter release at specific connections between neurons, known as synapses. By controlling gene expression on site, the neuron is able to rapidly regulate individual synapses. They found that this regulation is dynamic – local protein synthesis in axons is only required during periods when the neuron is highly active.

“This aspect of high-frequency activity is especially interesting, because short bursts of high activity have been linked to memory formation in the brain,” says Hovy Wong, PhD, a postdoctoral fellow with Professor Sjöström. “In previous work, the protein synthesis regulation on neurotransmission we found was largely overlooked because researchers examined low-frequency activation of synaptic connections.”

The researchers were also surprised to learn that this regulation only occurs at some synapse types. It influences excitation of excitatory cells but not excitation of inhibitory cells. This means local protein synthesis in an axon can selectively tune excitation-inhibition balance to ensure stability in the brain.

“This finding has important implications for how brain circuits manage to balance out excitation and inhibition,” adds Prof. Sjöström. “These processes often go awry in neurological disorders such as autism or Alzheimer’s disease. Improving our understanding can lead to important changes in the way we think about the role of axons in health and disease.”

About the study

Read the publication: Synapse specific burst coding sustained by local axonal translation in the journal Neuron. First published 8 November 2023 by Hovy Ho-Wai Wong, Alanna J. Watt, and P. Jesper Sjöström https://doi.org/10.1016/j.neuron.2023.10.011

The authors gratefully acknowledge support from Healthy Brains for Healthy Lives and the RI‑MUHC.