Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.
Sleep and Wake Coordinated by Glia
Philip Haydon, PhD, Professor at Tufts University
January 24, 2020
Fralin Biomedical Research Institute, Virginia Tech
Dr. Philip Haydon a pioneer in the field of astrocyte research. His lecture begins a description of his early lab days, where he admits to not applying for any grants in his first few years of being a professor as projects involving glia weren’t being funded. HIs group was the first to find that astrocytes, not neurons, release glutamate. He was also one of the authors on the first paper to coin the term “tripartite synapse,” which he notes was not well received by all scientists at the time of publication.
The majority of this seminar focuses on the role that astrocytes play in sleep and wakefulness. Astrocytes are a source of adenosine, which is one of the molecules responsible for the feeling of sleepiness. Using a transgenic mouse line expressing dnSNARE (a dominant-negative version of vesicular protein SNARE) that causes interference with exocytosis in astrocytes, Dr. Haydon’s lab found that sleep pressure was reduced. Even when these dnSNARE animals were sleep deprived, they did not show an increased desire to sleep or sleep for longer after being deprived.
With additional experiments it was found that D-serine, which is a co-agonist for neuronal NMDA receptors, can be astrocyte derived and is increased during times of wakefulness. This is known in part due to the fact that the dnSNARE animals show lower levels of D-serine due to the fact that its release from astrocytes is blocked. Additionally they show that cholinergic fibers active during wakefulness stimulate ACh receptors on astrocytes, which increases the D-serine levels and increases neuronal activity.
Astrocytes are not just acting as single cells, but form networks through gap junction coupling. When the connexin proteins that create these connections are knocked out, interesting changes in sleep occur. While there is no obvious difference in EEG activity, these animals exhibit a narcolepsy-like phenotype. Reduced neuronal excitability is seen in different brain regions, such as the cortex. Through the work of Dr. Hayden’s lab, it is now known that lactate can rescue this phenotype, as it is released from the astrocyte and shuttled into the neuron to become ATP.
I found Dr. Haydon to be a wonderfully engaging speaker. He frames his research in an accessible way, and throughout the seminar he shared advice he has learned throughout his career. He urged the young scientists in attendance to always consider if there is clinical relevance to the results you obtain, and stressed the importance of letting your data show you what is occurring instead of trying to force-fit a hypothesis to your results.
On a more personal note, I believe Dr. Haydon is a very inspiring person. At the age of 14 he developed TBI-induced epilepsy, and now has created a non-profit, Sail 4 Epilepsy, to raise awareness of epilepsy and inspire those who live with the condition to live their lives to the fullest. He is currently in the process of sailing around the globe and presenting his research to the public while on his journey. I would recommend that anyone interested in astrocytes check out his work!