New Pannexin 1 research could shed light on neurodevelopmental disorders

Just as mobile networks depend on complex devices like satellites to send and receive data, our brains rely on intricate cellular specializations called synapses to transmit information through large networks of brain cells. Within these networks, groups of co-activated neurons known as network ensembles represent the main output of the cerebral cortex, the site of key brain functions like thinking, perception, movement, planning, and many others.

The vast majority of these synapses are located at dendritic spines, minuscule structures at the receptive ends of brain cells. These dendritic spines form as our brain continues to develop after we are born.

Last week, a team from Dr. Leigh Anne Swayne’s lab published work in eNeuro showing that a protein called pannexin 1 (Panx1) regulates cortical neuron network ensembles and dendritic spine formation.

“Our new findings show that Panx1, a protein that act as a doorway for small molecules in brain cells, regulates how neuronal networks form by impacting how neurons form connections with each other,” says the study’s lead author, Dr. Juan Sanchez-Arias, a PhD student in the Division of Medical Science (DMSC) Neuroscience Graduate Program.

(L-R) Drs. Juan Sanchez-Arias and Leigh Anne Swayne

Other research groups working on Panx1 have mainly focused on the mature brain—namely on the hippocampus, a region controlling memory processing. However, since its inception in 2011, the Swayne Lab has pioneered work on the role of Panx1 in the development of brain cells. This is the first study focusing on the role of Panx1 in cortical development during the early postnatal period. The team discovered there is a dramatic drop in the levels of Panx1 at synapses during this time.

Dr. Sanchez-Arias investigated the consequences of deleting Panx1 from neurons, and found the number of network ensembles and dendritic spines increased. He detected these changes by performing calcium imaging and high-resolution microscopy of the structure of neurons labelled with a membrane-dye. This analysis was assisted by undergraduate student Sarah Ebert, while other team members—including former visiting scientist Dr. Mei Liu and MSc student Catherine Choi—contributed biochemical approaches. Those complementary approaches detected important changes in key proteins involved in synaptic function. collaborator and fellow DMSC researcher, Dr. Craig Brown, also provided support for the Swayne’s Lab first foray into dendritic spine research.

The team’s novel findings could shed new light on previous studies implicating Panx1 in neuropsychiatric disorders. Dendritic spine abnormalities (or, dysregulation) and synaptic dysfunction are hallmarks of multiple disorders, including autism spectrum disorder, schizophrenia, bipolar disorder, Rett syndrome and more. According to Swayne, studies investigating dendritic spine formation are important for making inroads into understanding diseases characterized by dendritic spine abnormalities. “Our limited understanding of the molecular events underlying dendritic spine formation is preventing us from harnessing this information clinically,” she says.

“Understanding the molecular events leading to dendritic spine formation, like the role of Panx1, is critical both for neuroscientists and healthcare providers,” agrees Dr. Sanchez-Arias.

The Swayne Lab would like to acknowledge funding from the Canadian Institutes of Health Research, the Scottish Rite Charitable Foundation of Canada, the Michael Smith Foundation for Health Research, the BC Schizophrenia Society Foundation, and the University of Victoria Donor Awards.

You can read the article in eNeuro here.