Mice that suffered from a lack of sleep increased the activity of inhibitory neurons in the hippocampus, thereby disrupting the processing and storage of new memories.
By: University of Michigan Translation: Gilat Simon
While there are students who think it's a good idea to study all night before an exam, the conventional objection to this is probably justified: a good night's sleep apparently helps you remember better, and thus prepare for the exam, according to a University of Michigan study.
Researchers Sarah Atton and James Delmore found that when mice suffer from a lack of sleep, there is an increase in the activity of inhibitory neurons in the hippocampus, a vital area of the brain that is responsible for navigation as well as processing and storing new memories.
"Since these neurons limit activity in their neighboring neurons, this physiological response interferes with the control of normal neuronal activity in the hippocampus," says Prof. Atton. "I always tell my students that a white night doesn't help them prepare for the exam..."
The results of the study were published in PNAS and the findings may have implications for human performance and learning strategies.
Previous research has shown that there is a sensitive window of time - several hours after learning - during which mice need to sleep to stabilize and strengthen a memory. During this period, the neural activity in the hippocampus must remain undisturbed, and RNA transcription and translation within the neurons must occur normally.
Studying before bed
Eton and Delmore investigated the possible relationship between changes in neural activity after learning and changes in the translation of their proteins.
First, Delmore studied the interaction between sleep and wakefulness, hippocampal neural activity and activity driven by the phosphorylation of S6, a component of ribosomes, those tiny organelles where translation of mRNA into protein occurs. This phosphorylation event apparently affects the mRNA that is translated into proteins when the neurons become more active. This regulation is apparently important for adapting to the frequently changing metabolic demands of the neurons.
Delmore gave mice a fear stimulus. When the mice were allowed to sleep freely after the stimulation, he saw that S6 phosphorylation increased in a part of the hippocampus called the dentate gyrus, the first area where memories are formed.
But when the mice were deprived of sleep, Delmore found that the level of phosphorylation decreased in the hippocampus. This decrease interfered with the formation of memories of the fear stimulus.
Delmore's next question was whether this reduction in S6 phosphorylation activity following sleep deprivation affects all neurons similarly. Using bioinformatics allowed a comparison of the amount of mRNAs associated with phosphorylated S6-containing ribosomes versus the mRNA profile under conditions of early sleep or total sleep deprivation.
The collected RNA was sequenced. The findings showed that after sleep deprivation, there was a significant increase in the amount of RNA transcripts of the type that is specifically present in interneurons that express the neuropeptide somatostatin as well as the inhibitory neurotransmitter GABA.
This relative increase suggests that increased activity among interneurons that contain somatostatin causes inhibition of the neighboring neurons as well as the total phosphorylation of S6, which acts to weaken the firing rate of all the neurons there.
The body's reaction against stressful memories
When they mimicked this inhibition mechanism in mice whose sleep was not interrupted, they were able to interfere with hippocampal activity and stabilize memories. Conversely, inhibiting the activity of somatostatin-expressing interneurons after learning increased the activity among dentate gyrus neurons and was beneficial for the stabilization of memories.
In diseases such as Alzheimer's, when sleep difficulties are common, there may be a connection between the physiological mechanism described in this study and memory loss. However, there may be a function that protects the neurons or an adaptive psychological response against stressful memories, says Prof. Atton.
Lack of sleep may in certain situations be curative. For example, using sleep deprivation after a traumatic event may be a way to prevent post-traumatic stress disorder.
This study opens possibilities to investigate how a change in the relative balance between the activity of amplifying neurons and inhibitory neurons affects memory, as well as a comparison of the effect of these mechanisms in REM sleep and non-REM sleep.
