Scientists have discovered a new daily rhythm

Using mouse models, the researchers discovered a new daily rhythm in a synapse that inhibits brain activity
.
These neural connections, called inhibitory synapses, rebalance as we sleep, allowing us to consolidate new information into lasting memories
.
The findings, published in the journal PLOS Biology, may help explain how subtle synaptic changes improve human memory
.
Researchers at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, led the study
.

"Inhibition is important
for all aspects of brain function.
But over the past two decades, most sleep research has focused on understanding excitatory synapses," said
senior researcher Dr.
Wei Lu.
"This is a timely study that attempts to understand how sleep and wakefulness regulate the plasticity
of inhibitory synapses.
"

Dr.
Kunwei Wu, a postdoc in Dr.
Lu's lab, studied what happens
to inhibitory synapses in mice during sleep and wakefulness.
Electrical recordings of neurons in the hippocampus, an area of the brain involved in memory formation, reveal a previously unknown pattern
of activity.
During wakefulness, stable "tonic" inhibitory activity increases, but rapid "staged" inhibitory activity decreases
.
They also found that activity-dependent enhancement of inhibitory electrical responses was much greater in awake mouse neurons, suggesting that waking states, rather than sleep, may strengthen these synapses
to a greater extent.

Inhibitory neurons use the neurotransmitter aminobutyric acid (GABA) to reduce the activity
of the nervous system.
These neurons release GABA molecules into the synaptic cleft, the space between neurotransmitters that diffuse between neurons, and inhibitory synapses
.
These molecules bind to GABAA receptors on the surface of nearby excitatory neurons, causing them to fire
less frequently.

Further experiments showed that changes in synapses during waking hours were driven
by an increase in the number of α5-GABAA receptors.
In awake mice, the activity-dependent enhancement of phase electrical responses is weakened when the receptor is
blocked.
This suggests that the accumulation of GABAA receptors in the awake state may be the key to building stronger, more effective inhibitory synapses, a fundamental process known as synaptic plasticity
.

"When you learn new information during the day, neurons are bombarded with excitatory signals from the cortex and many other areas of the brain
.
In order to convert this information into memory, you first need to regulate and perfect it, and that's where inhibition works
.
Dr.
Lu said
.

Previous studies have suggested that synaptic changes in the hippocampus may be driven by signals produced by inhibitory interneurons, a special type of cell that makes up only 10-20 percent
of neurons in the brain.
There are more than 20 different interneuron subtypes in the hippocampus, but recent studies have highlighted two types, parvalbumin and somatostatin, which play a key role
in synaptic regulation.

To determine which interneuron was responsible for their observed plasticity, Dr.
Lu's team used optogenetics, a technique that uses light to turn cells on or off, and found that wakefulness leads to more alpha5-GABAA receptors, as well as stronger connections
from parvalbumin (rather than somatostatin) interneurons.

Humans and mice have similar neural circuits
in memory storage and other basic cognitive processes.
This mechanism may be a way
to suppress input to precisely control the fluctuation of information between neurons and the entire brain network.

"Inhibition is actually very powerful because it allows the brain to function in a fine-tuned way, which is basically the basis of all cognition," Dr.
Lu said
.

Because inhibition is critical to almost every aspect of brain function, this study helps scientists understand not only the sleep-wake cycle, but also neurological disorders that stem from abnormal brain rhythms, such as epilepsy
.

In the future, Dr.
Lu's team plans to explore the molecular basis
of GABAA receptor transport to inhibitory synapses.

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