New Study Explores How Sleep Deprivation Inhibits Memory Consolidation

It is conventional wisdom that ensuring a good night’s sleep before a big day is critical to cognitive performance. Erratic sleep schedules and sleep loss affect learning and memory in children and adults alike. Scientists at the University of Michigan have proved as much and gone further to explain the neuronal circuitry that controls memory consolidation.

Memory and Sleep

According to previous studies, the brain needs an undisturbed and unstimulated window of time after a few hours of rigorous learning to consolidate all the inputs and convert them into relevant memories that can be retrieved at will. This can be achieved by sleeping at regular intervals.

To understand what happens in the learning-and-memory center of the brain, the hippocampus during sleep, Sara Aton and her team studied the neuronal activity, transcription, and translational changes, after learning in mice. The study was published in the journal Proceedings of the National Academy of Sciences.

S6 Phosphorylation Correlates to Learning and Sleep Deprivation

Mice, after a fear stimulus, were either allowed to sleep or sleep-deprived. The authors tested the two sets of mice for the phosphorylation status of S6, a component of the ribosome that translates mRNA into protein and differences in expression of neuron subtypes.

Phosphorylated S6 is implicated in translating mRNAs in activated neurons. In sleep-deprived mice, the levels of phosphorylated S6 in the hippocampus were low. Additionally, mice that underwent learning tasks demonstrated elevated levels of phosphorylated S6, indicating that learning increases and sleep loss decrease phosphorylated S6 in the hippocampus.

Sleep Loss–Driven Inhibitory Gate

Characterizing the class of neurons regulated by phosphorylated S6 by RNA sequencing, the authors found Sst+ interneurons as the driver which secrete somatostatin and GABA. These inhibitory neurotransmitters deactivate the surrounding pyramidal neurons in the hippocampus, important for memory acquisition and consolidation, rendering the circuit incomplete for creating new memories.

They were able to mimic disruption of hippocampal activity in sleeping mice by activating the Sst+ interneurons by increased cholinergic input. Based on these results, the authors propose a model where sleep deprivation activates the otherwise-inactive Sst+ interneurons due to increased expression of cholinergic neurons in the medial septum and orexinergic neurons in the lateral hypothalamus.

Associate professor in the University of Michigan, Department of Molecular, Cellular and Developmental Biology and lead author of the study, Aton, explained, “Because these neurons limit activity in their neighbors, this physiological response makes it impossible to muster normal neuronal activity in the hippocampal structure.”

More to the Puzzle

Interestingly, suppression of Sst+ interneurons in sleep-deprived mice, post-learning could not fully rescue memory consolidation, indicating that there may be other neuronal populations regulating memory or hippocampal activity in these sleep-deprived mice may not entirely resemble the activity of hippocampus in sleeping mice. Further studies would be required to address if other areas of the brain may also contribute to sleep-deprived neuronal activity. 

Understanding brain activity during sleep and the ability to excite or inhibit specific neurons to promote memory building in sleep is valuable. In the long term, it could be helpful to address cognitive and learning disorders. Sleeping disorders related to stress or trauma could be less damaging, where sleep loss could be managed to cause minimum cognitive loss. In neurological indications such as Alzheimer’s, memory loss could be limited by manipulating the underlying neuronal circuitry.

Related posts:

Latest Study on Neuronal Gene Expression May Shed Light on the Memory Formation Process Genetics Does Influence the Gut Microbiome, Long Term Research Reveals Harnessing the potential of CRISPR-Cas9 for Gut Microbiome Gene Editing Inside the Aging Brain: NTU Singapore’s Revelation on Memory Neuron Communication

Author

Sahana Shankar