Brain signals that help memories form may influence blood sugar

Date:
August 11, 2021
Source:
NYU Langone Health / NYU Grossman School of Medicine
Summary:
A set of brain signals known to help memories form may also
influence blood sugar levels, finds a new study in rats.



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


========================================================================== Researchers at NYU Grossman School of Medicine discovered that a
peculiar signaling pattern in the brain region called the hippocampus,
linked by past studies to memory formation, also influences metabolism,
the process by which dietary nutrients are converted into blood sugar
(glucose) and supplied to cells as an energy source.

The study revolves around brain cells called neurons that "fire"
(generate electrical pulses) to pass on messages. Researchers in recent
years discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles, with the firing pattern is called a "sharp wave ripple" for the shape it takes when captured graphically by
EEG, a technology that records brain activity with electrodes.

Published online in Natureon August 11, a new study found that clusters of hippocampal sharp wave ripples were reliably followed within minutes by decreases in blood sugar levels in the bodies of rats. While the details
need to be confirmed, the findings suggest that the ripples may regulate
the timing of the release of hormones, possibly including insulin, by
the pancreas and liver, as well of other hormones by 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 Gyo"rgy Buzsa'ki, MD, PhD, the Biggs Professor in the Department
of Neuroscience and Physiology at NYU Langone Health "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 Buzsa'ki,
also a faculty member in the Neuroscience Institute at NYU Langone.



========================================================================== Known to keep blood sugar at normal levels, insulin is released by
pancreatic cells, not continually, but periodically in bursts. As sharp
wave ripples mostly occur 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 seen in
type 2 diabetes, say the study authors.

Previous work by Buzsaki's team had suggested that the sharp wave ripples
are involved in permanently storing each day's memories the same night
during NREM sleep, and his 2019 study found that rats learned faster to navigate a maze 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, PhD, a post-doctoral scholar in Buzsaki's lab.

Dual Role The hippocampus is a good candidate brain region for multiple
roles, say the researchers, because of its wiring to other brain regions,
and because hippocampal neurons 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 hippocampal ripples
reduce blood glucose levels as part of such a loop.



========================================================================== "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.

The study data also suggest that hippocampal sharp wave ripple signals
are conveyed to hypothalamus, which is known to innervate and influence
the pancreas and liver, but through an intermediate brain structure
called the lateral septum. Researchers found that ripples may influence
the lateral septum just by amplitude (the degree to which hippocampal
neurons fire at once), not by the order in which the ripples are combined, which may encode memories as their signals reach the cortex.

In line with this theory, short duration ripples that occurred in
clusters of more 30 per minute, as seen during NREM sleep, induced a
decrease in peripheral glucose levels several times larger than isolated ripples. Importantly, silencing the lateral septum eliminated the impact
of hippocampal sharp wave ripples on peripheral glucose.

To confirm that hippocampal firing patterns caused the glucose
level decrease, the team used a technology called optogenetics to
artificially induce ripples by re-engineering hippocampal cells to
include light-sensitive channels.

Shining light on such cells through glass fibers induces ripples
independent of the rat's behavior or brain state (e.g. resting or
waking). Similar to their natural counterparts, the synthetic ripples
reduced sugar levels.

Moving forward, the research team will seek to extend its theory
that several hormones could be affected by nightly sharp wave ripples, including through work in human patients. Future research may also reveal devices or therapies that can adjust ripples to lower blood sugar and
improve memory, says Buzsaki.

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

========================================================================== Story Source: Materials provided by NYU_Langone_Health_/_NYU_Grossman_School_of_Medicine.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. David Tingley, Kathryn McClain, Ekin Kaya, Jordan Carpenter, Gyo"rgy
Buzsa'ki. A metabolic function of the hippocampal sharp wave-ripple.

Nature, 2021; DOI: 10.1038/s41586-021-03811-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210811131452.htm

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