Brain Star Award Winner Christina You Chien Chou

An optomapping approach to better understand connections in the visual cortex of the brain

In the brain, information is passed from neuron to neuron via connections called synapses. Synaptic dysfunction unsurprisingly underlies many neurological diseases, such as autism, schizophrenia, and epilepsy. Understanding how synapses are wired up in a cell-type-specific way is fundamental to understanding brain function. In this publication, Christina Chou, working in Jesper Sjöström’s research group at McGill University, used a new technique called optomapping to reveal previously unknown circuit wiring principles for excitatory and inhibitory neurons in mouse visual cortex. She found that different cell types have distinct connectivity patterns and that excitatory synapses onto inhibitory neurons are stronger, denser, and farther reaching than onto excitatory neurons. In other words, inhibition may win over and temper excitation. She additionally found that short-term synaptic dynamics depend on both input neuron location and on target cell type. These findings are key to understanding how the diversity of synapses underlie cell-type-specific circuit functions.

In the past, classic electrophysiology-based techniques have allowed researchers to precisely study synapses, but the low data yield of this technique has been a major obstacle towards comprehensive mapping of cell-type-specific connections in healthy and diseased states. As a result, there is a long-standing throughput problem in neuroscience research. In the lab of Prof. Jesper Sjöström, Christina Chou built a pipeline that combined electrophysiology and optogenetics for rapidly finding and studying synapses between different types of neurons without sacrificing precision and reliability. This method, which they called optomapping, is 100-fold faster than current electrophysiology-based techniques.

In this publication, Christina Chou optomapped synaptic connectivity at an unprecedented scale, demonstrating the value of optomapping as a new approach for charting neuronal circuits, enabling researchers to rapidly and reliably test hundreds of candidate synaptic connections spanning the entire cortical column. The research group has also made the code for data acquisition and data analysis freely available. By making use of relatively standard 2-photon microscopy equipment, optomapping allows medium-sized research groups to conduct in-depth investigation of synaptic connectivity, an undertaking that was previously only possible for large, well-funded institutes. It is a game-changing technique that is already reshaping how neuroscience research is done. This optomapping project also provided fresh perspective on the principles that govern fine wiring structure of the visual cortex. The ability to tease apart cell-type-specific circuit functions promises the development of more precise medicine for the treatment of neurological disorders in the future.

About Christina Chou

Dr. Christina Chou conducted this work as part of Prof. Jesper Sjöström’s research group, which explores cortical synapses and their plasticity using cutting-edge microscopy and electrophysiology techniques at McGill University. In this project, Christina Chou spearheaded the design, development, implementation, and validation of optomapping. Under Prof. Sjöström’s supervision, this study is the centrepiece of her doctoral dissertation.

Dr. Christina Chou is currently a medical writer at liV Medical Education Agency.

LinkedIn: https://www.linkedin.com/in/christinaycchou/

Source of Funding

• The Canadian Institutes for Health Research (CIHR)
• Natural Sciences and Engineering Council of Canada (NSERC)
• Canadian Foundation for Innovation (CFI)
• Fonds de recherche du Québec – nature et technologie (FRQNT)
• Fonds de recherche du Québec – santé (FRQS)
• Ann and Richard Sievers Award
• McGill Healthy Brains for Healthy Lives Initiative (HBHL)
• McGill Faculty of Medicine Max E. Binz Fellowship
• The Research Institute of the McGill University Health Centre (RI-MUHC)
• The Montreal General Hospital (MGH) Foundation
• Quebec Bio-imaging Network (QBIN)