Swayne Lab receives CIHR funding to study stabilization of nerve cell connections

Earlier this year, Dr. Leigh Anne Swayne (pictured left) received a five-year Project Grant totalling $902,700 for her project “Targeting pannexin 1 to tune dendritic spine stability” in the Canadian Institutes of Health Research (CIHR) 2023 Spring Project Grant competition.

Nerve cell connections, also called synapses, are initially dynamic, and they must stabilize to form the circuits that underlie proper brain function. Despite many advances, our picture of the molecular and cellular foundations of this process is incomplete. This prevents us from better understanding – and devising improved treatments for – neurological conditions in which synapse stability is impaired, such as chronic stress and schizophrenia. The outcomes of Dr. Swayne’s CIHR-funded research will help to bridge this critical brain health knowledge gap. 

This work builds on her lab’s discoveries related to pannexin 1, a protein enriched in developing neurons that forms channels in cell membranes and acts as a scaffold for key cellular signaling proteins. Pannexin 1 levels are high early in neuronal development, and they decrease as neurons mature and synapses stabilize. (The factors controlling this reduction in pannexin 1 levels are not known.) Dr. Swayne’s team recently discovered that pannexin 1 inhibits the stabilization of post-synaptic structures called dendritic spines. With this CIHR funding, her team is determining the precise molecular underpinnings of this inhibition process. Dr. Swayne predicts that pannexin 1 prevents synapse stabilization by physically sequestering key cellular signaling proteins until they are needed, acting as a sort of molecular “brake.” The team is also delving into the factors controlling the downregulation of neuronal pannexin 1, which enables the release of this molecular “brake” and allows spines to stabilize and circuits to form.

To test their predictions, the Swayne Lab and their collaborators are using a combination of tools to image the structure and function of nerve cell connections, the activity of nerve cells and their circuits, and the impacts on behaviour. Their findings will ultimately bridge critical gaps in the fundamental understanding of the role of pannexin 1 in synapse stabilization. Since pannexin 1 and its interacting proteins are linked to neurological diseases and disorders characterized by impaired synapse stability – such as chronic stress, depression, schizophrenia, and Alzheimer’s disease – the outcomes of this research will also have key implications for understanding circuit refinement in brain health and disease.

Annika Ariano (pictured right) is a new master’s student in the Swayne Lab whose graduate thesis work focuses on the factors controlling the downregulation of pannexin 1, a specific area within the larger CIHR-funded project. “I am excited to contribute to the already vast knowledge base of my amazing fellow Swayne Lab members and to help fill in the knowledge gaps that remain within my own graduate thesis research investigating control of neuronal pannexin 1 levels,” she says. “I found the surface-level knowledge of the nervous system’s functions, structures, and pathways that I gained throughout my undergraduate degree at the University of Guelph always left me wanting to learn more.”

Dr. Swayne is glad to have to opportunity to mentor superb trainees like Annika in her lab. “I was fortunate to recruit Annika from the University of Guelph, where I also completed my undergraduate studies. Annika first came to UVic to work in my lab in the summer of 2022 as an undergraduate researcher. She is a superstar. It is awesome to have her back in the lab, and she has definitely hit the ground running. I am very excited for what is to come with her graduate thesis research.”