Before the delivery of the neurotoxin (left) the SCN oscillate in a synchronized pattern. After the delivery of the neurotoxin (right), neurons in the SCN oscillate randomly. Credit: Image courtesy of the Doyle Lab
For the 1st time it has been shown how neurons in the SCN are connected to each other, shedding light on this vital area of the brain. Understanding this structure – and how it responds to disruption – is important for tackling illnesses like diabetes and PTSD. The scientists have also found that disruption to these rhythms such as shifts in work schedules or blue light exposure at night can negatively impact overall health. The suprachiasmatic nucleus makes everything in the body run on time and is the control center for circadian rhythms which regulate everything from sleep to hunger, insulin sensitivity, hormone levels, body temperature, cell cycles and more.
“The SCN has been so challenging to understand because the cells within it are incredibly noisy,” said John Abel, SEAS. “There are more than 20,000 neurons in the SCN, each of which not only generates their own autonomous circadian oscillations but also communicates with other neurons to maintain stable phase lengths and relationships. We were able to cut through that noise and figure out which cells share information with each other.”
The SCN looks like a miniature brain, with two hemispheres, inside the hypothalamus. It receives light cues from the retina to help it keep track of time and reset when necessary. When functioning probably, the neurons inside both hemispheres oscillate in a synchronized pattern. In order to understand the structure of the network, Abel and the team had to disrupt that pattern. The researchers used a potent neurotoxin commonly found in pufferfish to desynchronize the neurons in each hemisphere, turning the steady, rhythmic pulse of oscillations into a cacophony of disconnected beats. The team then removed the toxin and observed the network as it reestablished communication, using information theory to figure out which cells had to communicate to resynchronize the whole network.
By observing the SCN at single-cell resolution, Abel and the team identified a core group of very friendly neurons in the center of each hemisphere that share a lot of information during resynchronization. They also observed dense connections between the hubs of each hemisphere. The neurons outside these central hubs, ie shell, behaved more like acquaintances than friends, sharing little information amongst themselves.
“We’ve assumed that the neurons in the shell communicated to synchronize that rhythm but our research suggests that phase clustering in the shell is actually mediated by the core neurons.” By using the neurotoxin to disrupt circadian rhythms, Abel and the team demonstrated that the core is the key to resynchronization even without light cues.
“For the last 15 years our group has been studying the complex control mechanisms that are responsible for the generation of robust circadian rhythms in the brain,” said Frank Doyle, the John A. Paulson Dean and John A. & Elizabeth S. Armstrong Professor of Engineering & Applied Sciences, who co-authored the paper. “This work brings us one step closer to reverse engineering those paradigms by elucidating the topology of communication amongst neurons, thus demonstrating the importance of a systems perspective to link genes to cells to the SCN tissue.” https://www.seas.harvard.edu/news/2016/05/mapping-circuit-of-our-internal-clock
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