Research summary
The human brain is an extraordinary network of trillions of synapses—microscopic junctions that allow neurons to communicate, learn and adapt. Understanding how these synapses form, function and remodel with experience is central to explaining how we think, remember and feel.
Dr. Tabrez J. Siddiqui’s research program seeks to decode the molecular logic of synapse organization and the principles that enable neurons to form precise, enduring and adaptable connections. His laboratory investigates how molecular systems bridging pre- and postsynaptic membranes align neurotransmitter release with receptor activation to ensure efficient, reliable and flexible communication. These trans-synaptic mechanisms are fundamental to the formation and plasticity of neural circuits and are increasingly recognized as key contributors to the pathophysiology of neurodevelopmental and psychiatric disorders.
To address these questions, the Siddiqui Lab combines molecular, cellular, systems and computational approaches, employing biochemical, genetic, proteomic, electrophysiological, imaging, anatomical and behavioural methods to relate molecular interactions to synaptic architecture and function. A central focus is on the nanoscale organization of neurotransmitter receptors within the postsynaptic membrane and how their alignment with presynaptic release sites determines the strength and adaptability of synaptic transmission. This integrative framework has revealed that precise molecular coordination is essential for maintaining synaptic integrity and that its disruption produces the structural and functional abnormalities characteristic of disorders such as autism and schizophrenia.
Supported by the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Foundation for Innovation (CFI), the Siddiqui group aims to define the principles governing synapse formation and receptor organization, uncover pathway-specific mechanisms of plasticity and determine how genetic alterations in these processes compromise neural circuitry. The long-term goal of this work is to translate molecular insights into strategies that restore synaptic function and cognitive health. Together, these studies connect molecular architecture to circuit behaviour, advancing both fundamental neuroscience and the development of targeted therapies for brain disorders.
Research interests
- Autism spectrum disorder and neurodevelopmental connectivity defects
- Mechanisms underlying synaptic plasticity
- Molecular mechanisms of synapse formation and maintenance
- Neurotransmitter receptor organization and signaling efficiency
- Schizophrenia and cortical-thalamic network disorganization
All of these areas reflect a unifying goal: understanding how molecular architecture creates the basis of cognition and how repairing that architecture can restore mental health.
Research affiliations
Principal investigator, PrairieNeuro Research Centre, Kleysen Institute for Avanced Medicine, Health Sciences Centre
Reserch scientist, Children’s Hospital Research Institute of Manitoba (CHRIM)