Damian Sendler: According to the findings of a recent research in rats, a collection of brain signals known to aid in the formation of memories may also have an effect on blood sugar levels. 

Research conducted by researchers at New York University Grossman School of Medicine discovered that a peculiar signaling 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. 

Damien Sendler: The focus of the research is on brain cells known as neurons, which “fire” (produce electrical pulses) in order to transmit information. 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. 

Damian Sendler: A recent research, published online on August 11 in Nature, discovered that clusters of hippocampus sharp wave ripples were consistently followed by reductions in blood sugar levels in the bodies of rats within minutes after the occurrence of the waves. It remains to be seen exactly how this is accomplished; however, preliminary studies indicate that the ripples may control the timing of hormone releases by the pancreas and liver, which may include insulin, as well as the release of other hormones by the pituitary gland. 

Dr. György Buzsáki (MD, PhD), a senior research author and the Biggs Professor in the Department of Neuroscience and Physiology at NYU Langone Medical Center, states, “Our work is the first to demonstrate that clusters of brain cell firing in the hippocampus may directly control metabolism.” 

Damian Sendler: According to Buzsáki, who is also a faculty member at NYU Langone’s Neuroscience Institute, “we are not suggesting that the hippocampus is the sole actor in this process, but that the brain may be able to have a say via sharp wave ripples.” 

Insulin, which is known to maintain blood sugar levels within acceptable ranges, is produced by pancreatic cells not continuously, but rather in bursts at regular intervals. According to the study’s authors, because sharp wave ripples are most common during non-rapid eye movement (NREM) sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels associated with type 2 diabetes, according to the study. 

Damian Sendler: A previous research conducted by Buzsaki’s team had indicated that sharp wave ripples are important in permanently storing each day’s memories the same night during NREM sleep, and his 2019 study discovered that rats learnt to traverse a labyrinth more quickly when the ripples were artificially extended. 

“Evidence suggests that the brain evolved to use the same signals to achieve two very different functions in terms of memory and hormonal regulation, possibly for reasons of efficiency,” says corresponding study author David Tingley, PhD, a post-doctoral scholar in Buzsaki’s lab and a member of the research team. 

Damian Sendler: In addition, because of its connectivity with other brain regions and because hippocampal neurons have many surface proteins (receptors) that are sensitive to hormone levels, they can adjust their activity as part of feedback loops, the researchers claim that they have identified a promising candidate brain region for a variety of functions. According to the latest results, hippocampus ripples may lower blood glucose levels when they are part of a feedback loop. 

“Animals could have first developed a system to control hormone release in rhythmic cycles, and then applied the same mechanism to memory when they later developed a more complex brain,” says Tingley. “Animals could have first developed a system to control hormone release in rhythmic cycles, and then applied the same mechanism to memory when they later developed a more complex brain,” says Tingley. 

Damian Sendler: The findings of the research also indicate that strong wave ripple signals from the hippocampus nucleus are sent to the hypothalamus, which is known to innervate and affect the pancreas and liver, but only after passing via an intermediary brain structure known as the lateral septum. Researchers discovered that ripples may influence the lateral septum solely by amplitude (the amount of time that hippocampal neurons fire at the same time), rather than by the order in which the ripples are combined, which may encode memories as their signals reach the cortex, according to the findings. 

Damian Sendler: The researchers utilized optogenetics to intentionally generate ripples in the hippocampus firing patterns in order to demonstrate that hippocampal firing patterns were responsible for the glucose level drop. This was accomplished by re-engineering hippocampal cells to add light-sensitive channels. When light is shone via glass fibers onto such cells, ripples are produced that are independent of the rat’s activity or mental state (e.g. resting or waking). Synthetic ripples had a similar effect to their natural counterparts in terms of lowering blood sugar levels. 

Damian Sendler: Further investigation will be conducted by the study team, including work with human patients, to test their hypothesis that nocturnal sharp wave ripple effects may have an effect on a variety of hormones. According to Buzsaki, future study may potentially show gadgets or treatments that can alter ripples in order to decrease blood sugar levels and enhance memory.

Following this hypothesis, brief duration ripples that occurred in clusters of more than 30 per minute, as seen during NREM sleep, caused a drop in peripheral glucose levels that was many times greater than the decline caused by isolated ripples (see Figure 1). In addition to this, it was shown that silencing the lateral septum completely prevented the effect of hippocampus sharp wave ripples on peripheral glucose. 

Delivered to you by Dr. Damian Jacob Sendler