Category: Awards

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.

Read the full story here: https://can-acn.org/brain-star-award-winner-christina-you-chien-chou/

Read the original research article: Chou, C. Y. C., Wong, H. H. W., Guo, C., Boukoulou, K. E., Huang, C., Jannat, J., Klimenko, T., Li, V. Y., Liang, T. A., Wu, V. C., & Sjöström, P. J. (2024). Principles of visual cortex excitatory microcircuit organization. The Innovation, 6(1), 100735. DOI: 10.1016/j.xinn.2024.100735

https://doi.org/10.1016/j.xinn.2024.100735

A new framework to assess placement of electrodes in the brain for epilepsy surgery

Epilepsy is a chronic condition that is characterized by spontaneous recurring seizures. In clinical practice, the region which generates seizures is called the epileptic focus. The location of the focus can be localized by electrical measurement of brain activity, known as electroencephalography (EEG). This can be noninvasively placed on the scalp or invasively inserted into the brain for improved spatial accuracy. 30-40% of patients with epilepsy do not respond to antiseizure medication. For these patients a surgical intervention to remove the focus might be the only way to prevent seizures from occurring. However, currently only half of patients selected for surgery achieve post-operative seizure freedom. One reason may be due to the poor coverage of invasive electrodes in the brain tissue responsible for generating seizures. Research led by Kassem Jaber, working under the supervision of Dr. Birgit Frauscher at the Montreal Neurological Institute, resulted in the development of a spatial perturbation framework that evaluates whether invasive electrodes placed during pre-surgical evaluation adequately cover the epileptic focus.

Read the full story: https://can-acn.org/brain-star-award-winner-kassem-jaber/

Read the original scientific publication: Jaber, K., Avigdor, T., Mansilla, D., Ho, A., Thomas, J., Abdallah, C., Chabardes, S., Hall, J., Minotti, L., Kahane, P., Grova, C., Gotman, J. and Frauscher, B., 2024. A spatial perturbation framework to validate implantation of the epileptogenic zone. Nature Communications, 15(1), p.5253. https://rdcu.be/d6hnY

Identification of CD33m as a new protective factor in Alzheimer’s Disease development.

Immune cells in the brain, called microglia, are thought to be critical in Alzheimer’s disease (AD) development through numerous functions, including their ability to remove amyloid beta (Aβ), which is protein that accumulates in the brains of AD patients. In this study, Ghazaleh Eskandari-Sedighi, working in Matthew Macauley’s laboratory at the University of Alberta, focused on understanding the mechanism of action of a protein called CD33, which has been identified as one of the top-ranked drivers in the development of AD and that is predominantly found in microglia in the brain. By transferring different versions (called isoforms) of this protein in a mouse model of AD, they were able to show that these different isoforms have opposite effects on microglial cells and AD progression.

CD33 is a receptor that modulates immune response that exists in two forms:  a long isoform CD33M (Major) and a short isoform: CD33m (minor). Understanding how CD33 isoforms differentially impact microglial cell function has been challenging due to functional divergence between CD33 from mouse and humans. In this study, the researchers introduced the human CD33 gene in a mouse model of AD, which accumulates Aβ protein. In these mice, they found that CD33 isoforms have opposing effects on the response of microglia to Aβ accumulation. The larger CD33M increases the total level of Aβ and formation of plaques with a diffuse nature, which correlates with fewer number of microglia as well as higher number of dysfunctional neurons. In contrast, CD33m gives rise to opposite outcomes; beyond decreasing total Aβ levels, CD33m skews formation of compact Aβ deposits, correlating with increased microglia and fewer dysfunctional neurons. Overall, this work reveals how CD33, as a top genetic susceptibility factor for AD, is connected to microglial cell function.

Read the full story here: https://can-acn.org/brain-star-award-winnerghazaleh-eskandari-sedighi/

Scientific publication: Eskandari-Sedighi, G., Crichton, M., Zia, S. et al. Alzheimer’s disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice. Mol Neurodegeneration 19, 42 (2024).

https://doi.org/10.1186/s13024-024-00734-8

Better understanding the role of vision in the brain’s representation of space by studying freely moving primates

The hippocampus is a structure of the mammalian brain that has been implicated in spatial memory and navigation. Its role has been primarily studied in nocturnal mammals, such as rats, that lack many adaptations for daylight vision. Here, Diego B. Piza, working in the laboratory of Julio Martinez-Trujillo at Western University, demonstrates that during 3D navigation, the common marmoset, a New World primate adapted to daylight, uses different exploration–navigation strategies compared to rats. He further shows that maps of space in the marmoset brain depend on vision-related cues and object relationships used as landmarks for navigation. It is likely that similar encoding mechanisms exist in other diurnal mammals, including humans.

To explore their environment, marmosets predominantly use rapid head-gaze shifts for visual exploration while remaining stationary. During active movement, marmosets stabilize their head, in contrast to rats, who use low-speed head movements to scan the environment as they locomote. This work suggests that spatial memory in primates may rely on anchoring sequences of views to specific places, providing a unique mechanism for encoding spatial experiences.

This publication represents a major technical and conceptual achievement in neuroscience.

Read the full story: https://can-acn.org/brain-star-award-winner-diego-b-piza/

Article citation

Piza, D.B., Corrigan, B.W., Gulli, R.A., Do Carmo, S., Cuello, A.C., Muller, L., Martinez-Trujillo, J. Primacy of vision shapes behavioral strategies and neural substrates of spatial navigation in marmoset hippocampus. Nat Commun 15, 4053 (2024). https://doi.org/10.1038/s41467-024-48374-2

https://doi.org/10.1038/s41467-024-48374-2

Better understanding how ensembles of neurons are recruited in memory formation.

The hippocampus is a critical brain region for encoding and recall of episodic memories. The physical trace left in the brain by memory formation is called an ‘engram’, and the process by which new engrams are formed is still unclear. In this work, Andrew Mocle, working in the laboratory of Sheena Josselyn, used advanced imaging techniques to track neurons and their patterns of activity before, during, and after memory encoding. The resulting data prompted a new engram formation model, whereby small ensembles of neurons (instead of individual cells) are allocated to an engram depending on their average excitability at the time of learning. The demonstration that highly-excitable ensembles are preferentially allocated to encode newly learned information represents a major conceptual advance in the study of how memories are stored in the brain.

Read more: https://can-acn.org/brain-star-award-winner-andrew-mocle/

Featured scientific publication: Mocle, Andrew J., Adam I. Ramsaran, Alexander D. Jacob, Asim J. Rashid, Alessandro Luchetti, Lina M. Tran, Blake A. Richards, Paul W. Frankland, and Sheena A. Josselyn. “Excitability Mediates Allocation of Pre-Configured Ensembles to a Hippocampal Engram Supporting Contextual Conditioned Threat in Mice.” Neuron 112, no. 9 (May 1, 2024): 1487-1497.e6.

https://doi.org/10.1016/j.neuron.2024.02.007