Researchers link brain memory signals to blood sugar

A set of brain signals known to help form memories may also influence blood sugar levels, according to a new study in rats.

Researchers at the NYU Grossman School of Medicine have found that a particular signaling pattern in the region of the brain called the hippocampus, linked by previous studies to memory formation, also influences metabolism, the process by which food nutrients are converted into blood sugar (glucose) and supplied to cells for energy.

The study revolves around brain cells called neurons that “pull” (generate electrical impulses) to transmit messages. In recent years, researchers have found that populations of hippocampal neurons trigger within milliseconds of each other in cycles, the trigger pattern being referred to as “net wave ripple” for the form it takes when ‘it is captured graphically by EEG, a technology that records brain activity with electrodes.

Posted online in Nature On August 11, a new study found that clusters of high hippocampal wave ripples were reliably followed within minutes by decreases in blood sugar levels in the bodies of rats. Although the details need to be confirmed, the results suggest that the ripples may regulate the timing of the release of hormones, possibly including insulin, from the pancreas and liver, as well as other hormones from the pituitary gland.

“Our study is the first to show how clusters of brain cells triggered in the hippocampus can directly regulate metabolism,” says lead author of the study, György Buzsáki, MD, Ph.D., Biggs professor in the department of Neuroscience and Physiology from NYU Langone. Health

“We’re not saying that the hippocampus is the only player in this process, but that the brain can have a say through ripples of sharp waves,” says Buzsáki, also a faculty member at NYU’s Neuroscience Institute. Langone.

Known to keep blood sugar at normal levels, insulin is released by pancreatic cells not continuously, but periodically in bursts. Since high-wave ripples mainly occur during non-rapid eye movement sleep (NREM), the impact of sleep disturbances on high-wave ripples may provide a mechanical link between poor sleep and elevated rates of sleep. blood sugar levels seen in type 2 diabetes, say the study’s authors.

Earlier work by Buzsaki’s team had suggested that acute wave ripples are involved in the permanent storage of memories of each day on the same night during NREM sleep, and his 2019 study found that rats learned more quickly to navigate a labyrinth when the ripples were extended experimentally.

“The evidence suggests that the brain has evolved, for efficiency reasons, to use the same signals to perform two very different functions in terms of memory and hormone regulation,” says corresponding study author David Tingley, Ph.D., post-doctoral researcher. in Buzsaki’s laboratory.

Dual role

The hippocampus is a good candidate region of the brain for multiple roles, researchers say, because of its wiring to other areas of the brain, and because neurons in the hippocampus have many surface proteins (receptors). sensitive to hormone levels, so they can adjust their activity as part of feedback loops. The new findings suggest that the hippocampal ripples reduce blood glucose levels as part of such a loop.

“The animals would have first developed a system to control the release of hormones in rhythmic cycles, but then applied the same mechanism to memory when they later developed a more complex brain,” Tingley adds.

Data from the study also suggests that the acute wave ripple signals from the hippocampus are transmitted to the hypothalamus, which is known to innervate and influence the pancreas and liver, but through an intermediate brain structure called the lateral septum. Researchers have found that ripples can influence the lateral septum only by amplitude (the degree to which hippocampal neurons fire at the same time), and not by the order in which ripples are combined, which can encode memories when their signals reach the cortex.

According to this theory, short-lived ripples that occurred in clusters of over 30 per minute, as seen during NREM sleep, induced a decrease in peripheral glucose levels several times greater than isolated ripples. Importantly, the silence of the lateral septum eliminated the impact of the high wave ripples from the hippocampus on peripheral glucose.

To confirm that hippocampal triggering patterns caused glucose levels to decrease, the team used a technology called optogenetics to artificially induce ripples by rearranging cells in the hippocampus to include light-sensitive channels. Shining light on such cells through glass fibers induces ripples independent of rat behavior or brain state (e.g. at rest or awake). Similar to their natural counterparts, synthetic ripples have reduced sugar levels.

In the future, the research team will seek to expand their theory that several hormones may be affected by nighttime acute wave ripples, including through work in human patients. Future research could also reveal devices or therapies that can adjust ripples to lower blood sugar and improve memory, Buzsaki says.

Along with Tingley and Buzsaki, the study authors were Ekin Kaya, Kathryn McClain, and Jordan Carpenter of NYU Langone Health. The work was funded by grants from the National Institutes of Health MH122391, U19 NS104590, and U19NS107616.