The new study conducted by the researchers at New York University Grossman School of Medicine discovered that a peculiar signalling pattern in the brain region known as the hippocampus, which has previously been linked to memory formation, also influences metabolism, which is the process by which dietary nutrients are converted into blood sugar (glucose) and supplied to cells as a source of energy.
The focus of the research is on brain cells known as neurons, which “fire” (generate electrical pulses) in order to transmit messages. Scientists have recently discovered that populations of hippocampal neurons fire in cycles within milliseconds of each other, with the firing pattern being referred to as a “sharp wave ripple” because of the shape it takes when captured graphically by EEG, a technology that records brain activity with electrodes.
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The findings demonstrated that clusters of hippocampal sharp wave ripples were consistently followed by decreases in blood sugar levels in rats’ bodies within minutes. While the details remain unknown, the findings suggest that ripples may regulate the timing of hormone release from the pancreas and liver, as well as from the pituitary gland.
“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” says senior study author György Buzsáki.
“We are not saying that the hippocampus is the only player in this process, but that the brain may have a say in it through sharp wave ripples,” says Buzsáki.
Insulin, which is known to maintain normal blood sugar levels, is released intermittently by pancreatic cells. As sharp wave ripples occur primarily during non-rapid eye movement (NREM) sleep, the authors speculate that the effect of sleep disruption on sharp wave ripples may provide a mechanistic link between inadequate sleep and high blood sugar levels associated with type 2 diabetes.
Buzsaki’s previous research suggested that sharp wave ripples are involved in permanently storing each day’s memories during NREM sleep, and his 2019 study discovered that rats learned to navigate a maze more quickly when ripples were experimentally prolonged.
“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” says corresponding study author David Tingley.
According to the researchers, the hippocampus is an excellent candidate brain region for multiple functions because of its connectivity to other brain regions and because hippocampal neurons have numerous surface proteins (receptors) that are sensitive to hormone levels and can adjust their activity as part of feedback loops. The new findings suggest that hippocampal ripples contribute to this loop by lowering blood glucose levels.
“Animals could have first developed a system to control hormone release in rhythmic cycles, but then applied the same mechanism to memory when they later developed a more complex brain,” adds Tingley.
Additionally, the study’s findings indicate that hippocampal sharp wave ripple signals are transmitted to the hypothalamus, which is known to innervate and influence the pancreas and liver, but via an intermediate brain structure called the lateral septum. The researchers discovered that ripples can influence the lateral septum solely through their amplitude (the rate at which hippocampal neurons fire simultaneously), not through their order of the combination, which may encode memories as their signals reach the cortex.
According to this theory, short duration ripples occurring in clusters of more than 30 per minute, as observed during NREM sleep, induced a significant decrease in peripheral glucose levels several times greater than isolated ripples. Notably, by silencing the lateral septum, the effect of hippocampal sharp wave ripples on peripheral glucose was eliminated.
To establish that hippocampal firing patterns were responsible for the glucose level decrease, the researchers used a technique called optogenetics to artificially induce ripples in hippocampal cells by reengineering them to include light-sensitive channels.
Shining light through glass fibres onto such cells, ripples are produced regardless of the rat’s behaviour or brain state (e.g. resting or waking). Synthetic ripples, like their natural counterparts, reduced blood sugar levels.
The research team will continue to test its theory that nightly sharp wave ripples can affect several hormones, including work with human patients.
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Buzsaki adds that future research may reveal devices or therapies that can adjust ripples to help lower blood sugar and improve memory.
Image Credit: Getty