Canada Brain Power

Category: Expertise

  • Discovery of a new therapeutic avenue to protect vision in diabetic patients

    Discovery of a new therapeutic avenue to protect vision in diabetic patients

    This is a Brain Star Award feature of Dr. Sergio Crespo-Garcia, from the Maisonneuve-Rosemont Hospital Research Center. Dr. Crespo-Garcia he is first place winner of the 2024 competition and also the winner of the Marlene-Reimer Award for 2024. Congratulations!

    Diabetes is a silent epidemic with profound complications in the retina, including a profound visual impairment that robs individuals of their ability to connect with the world around them. Dr. Sergio Crespo-Garcia, working as a post-doctoral fellow in the laboratory of Dr. Przemyslaw (Mike) Sapieha at the Maisonneuve-Rosemont Hospital Research Center, has identified a novel therapeutic strategy aimed at reversing diabetic macular edema (DME), a pervasive blinding condition in diabetic patients. This new therapeutic approach has the potential to be applied to other neurodegenerative diseases.

    Specifically, Dr. Crespo-Garcia and his colleagues investigated the role of cell aging (senescence) in the development of diabetic macular edema (DME). They showed that senescent cells play a critical role in driving leakage from blood vessels and neuroinflammation of the retina leading to retinal damage in diabetes. Further, they identified a protein, called B-cell lymphoma extra-large (BCL-xL), as a potential target to selectively eliminate senescent cells. By employing foselutoclax (UBX1325), a small molecule drug, they demonstrated reduction in retinal neuroinflammation and improvement in vascular and neuronal function. Importantly, these preclinical data translated to human trials where patients enrolled in the Phase 1 trial showed a gain in visual acuity – these were patients for whom other treatments were no longer beneficial. Most excitingly, Phase 2 trials are currently underway, and could transform the way we protect vision in diabetic patients.

    Read the full story here: https://canadabrainpower.com/brain-star-award-winner-sergio-crespo-garcia/

    Read the full scientific publication here:

    Crespo-Garcia S, Fournier F, Diaz-Marin R, Klier S, Ragusa D, Masaki L, Cagnone G, Blot G, Hafiane I, Dejda A, Rizk R, Juneau R, Buscarlet M, Chorfi S, Patel P, Beltran PJ, Joyal JS, Rezende FA, Hata M, Nguyen A, Sullivan L, Damiano J, Wilson AM, Mallette FA, David NE, Ghosh A, Tsuruda PR, Dananberg J, Sapieha P. Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results. Nature Medicine 2024 Feb;30(2):443-454. doi: 10.1038/s41591-024-02802-4. Epub 2024 Feb 6. PMID: 38321220.

    https://www.nature.com/articles/s41591-024-02802-4

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

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

    This is a Brain Star Award Feature: Christina You Chien Chou – McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    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

  • Studying how the deepest regions of the brain contribute to brain activity

    Studying how the deepest regions of the brain contribute to brain activity

    This is a Brain Star Award Feature: Justine Hansen, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    The brainstem is a structure which is crucial for survival and consciousness, yet it is typically excluded from live human brain mapping efforts due to the difficulties in recording and analysing activity in this small region which sits deep at the base of the brain. In this study, Justine Hansen, working in the laboratory of Bratislav Misic at McGill University, used high-resolution 7-Tesla functional magnetic resonance imaging (fMRI) alongside new brainstem-specific processing and acquisition protocols to better understand connections in and with this essential brain region. This work identified a compact set of integrative hubs in the brainstem with widespread connectivity with the brain cortex. Specifically, they identified five modules of brainstem nuclei with distinct patterns of functional connectivity to the brain cortex related to memory, cognitive control, multisensory coordination, perception and movement, and emotion. These results push our understanding of brainstem functional neuroanatomy, such that the brainstem is no longer thought to simply be involved in basal functions but instead is recognized as an essential element of higher-order brain function.

    Read the full story here: https://can-acn.org/brain-star-award-winner-justine-hansen-2/

    Read the original research article here:

    Hansen, J. Y., Cauzzo, S., Singh, K., García-Gomar, M. G., Shine, J. M., Bianciardi, M., & Misic, B. (2024). Integrating brainstem and cortical functional architectures. Nature Neuroscience, 1-12.

    https://www.nature.com/articles/s41593-024-01787-0

  • Identification of the Pannexin-1 channel in the brain as a target to treat opioid withdrawal symptoms

    Identification of the Pannexin-1 channel in the brain as a target to treat opioid withdrawal symptoms

    Brain Star Award feature: Erika Harding, Nicole Burma, Charlie Hong Ting Kwok, University of Calgary, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Opioids remain one of the most effective analgesics, with 10-15% of Canadians receiving opioid prescriptions per year. However, opioids are also highly associated with substance use disorders and overdose related deaths. Last year alone, over 7000 Canadians passed away from opioid overdose related complications. Many people who start with an opioid prescription enter a feedforward cycle of use reinforced by significant withdrawal symptoms. Patients report these symptoms as so aversive they will do anything to avoid them, and current treatments for opioid use disorder have a high degree of relapse. There is a clear need for better treatments of opioid withdrawal.

    Research done by Drs. Erika Harding, Charlie Hong Ting Kwok and Nicole Burma in the laboratory of Dr. Tuan Trang at the University of Calgary has identified a channel called Pannexin-1, present in a brain area called the Locus Coeruleus as a potential target to alleviate opioid withdrawal symptoms.

    Read the full story here: https://can-acn.org/brain-star-award-winners-erika-harding-charlie-kwok-and-nicole-burma/

    Read the original scientific publication:

    Kwok CHT*, Harding EK*, Burma NE*, Markovic T, Massaly N, van den Hoogen NJ, Stokes-Heck S, Gambeta E, Komarek K, Yoon HJ, Navis KE, McAllister BB, Canet-Pons J, Fan C, Dalgarno R, Gorobets E, Papatzimas JW, Zhang Z, Kohro Y, Anderson CL, Thompson RJ, Derksen DJ, Morón JA, Zamponi GW, Trang T. Pannexin-1 channel inhibition alleviates opioid withdrawal in rodents by modulating locus coeruleus to spinal cord circuitry. Nat Commun. 2024 Jul 24;15(1):6264. doi: 10.1038/s41467-024-50657-7. PMID: 39048565

    https://www.nature.com/articles/s41467-024-50657-7

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

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

    Brain Star Award Feature: Kassem Jaber, Montreal Neurological Institute, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    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.

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

    Brain Star Award Feature: Ghazaleh Eskandari-Sedighi, University of Alberta, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    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

  • Discovery of differences in encoding threat discrimination in the brain of males and females

    Discovery of differences in encoding threat discrimination in the brain of males and females

    Brain Star Award Feature: Jessie Muir and Eshaan Sriram Iyer, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Learning to predict threat is essential, but equally important—yet often overlooked—is learning about the absence of threat. This study by Drs. Jessie Muir and Eshaan Sriram Iyer, working in the laboratory of Dr. Rosemary Bagot at McGill University, looks at mechanisms of threat encoding and discrimination in pathways relevant to depressive-like symptoms in mice. They identified sex differences in the circuits and mechanisms responsible for recognizing threats and suggest they may reflect differences in behavioral strategies that can be relevant for understanding sex differences in risk of psychiatric disorders.

    Depression is currently the leading cause of disability worldwide yet current antidepressant treatments remain ineffective in around 50% of the population. Women are twice as likely to develop depression compared to men. Given most pre-clinical studies have looked exclusively at males, there is a large gap in knowledge in the mechanisms underlying the disorder in females. Depression involves a disruption in many adaptive behavioral processes including discriminating aversive from neutral events.

    Read the full story here: https://can-acn.org/brain-star-award-winners-jessie-muir-and-eshaan-sriram-iyer/

    Featured scientific publication:

    Jessie Muir, Eshaan S. Iyer, Yiu-Chung Tse, Julian Sorensen, Serena Wu, Rand S. Eid, Vedrana Cvetkovska, Karen Wassef, Sarah Gostlin, Peter Vitaro, Nick J. Spencer & Rosemary C. Bagot Sex-biased neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior. Nature Neuroscience 27, 1966–1976 (2024). https://doi.org/10.1038/s41593-024-01748-7

    https://doi.org/10.1038/s41593-024-01748-7

  • A reduction in the number of connexions between brain cells is seen in the early stages of psychosis and is associated with negative symptoms.

    A reduction in the number of connexions between brain cells is seen in the early stages of psychosis and is associated with negative symptoms.

    Brain Star Award Feature: Maira Belen Blasco, Douglas Research Institute, McGill University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    Schizophrenia is a complex psychiatric disorder typically emerging in adolescence or early adulthood. It is thought to occur because of alteration in the maturation or pruning of connexions between neurons called synapses. While this theory, called the synaptic theory is supported by genetic, stem cell and studies of brain of deceased patients, direct evidence to support this theory in living patients was doubtful. Maira Belen Blasco, working in the laboratory of Dr. Romina Mizrahi at the Douglas Research Centre, McGill University, investigated whether difference in the density of synapses could be seen in first-episode psychosis (FEP) and in clinical high risk (CHR) patients using positron emission tomography (PET). They found that synaptic density was reduced during the early stages of psychosis and its risk states and associated with negative symptoms.

    Read the full story here: https://canadabrainpower.com/brain-star-award-winner-maira-belen-blasco/

    Featured scientific articleMaira Belen Blasco

    Blasco MB, Nisha Aji K, Ramos-Jiménez C, Leppert IR, Tardif CL, Cohen J,  Pablo M Rusjan , Romina Mizrahi. Synaptic Density in Early Stages of Psychosis and Clinical High Risk. JAMA Psychiatry. 2024 Nov 13; Published online: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2825648

    https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2825648

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

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

    Brain Star Award winner feature: Diego B. Piza, Western University, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    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.

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

    Brain Star Award Feature: Andrew Mocle, University of Toronto, won this prize based on the excellence of the research and its potential benefits to the health of Canadians. Brain Star Awards are presented by the Canadian Association for Neuroscience (CAN) and the Canadian Institutes of Health’s Institute of Neurosciences, Mental Health and Addiction

    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