Graham Diering, a researcher and postdoctoral fellow at the Johns Hopkins University School of Medicine, recently led a study which demonstrated the importance of sleep in new memory storage and formation. The study used mice as subjects, but the evidence gathered can be used to make insights about the human brain.

The brain brain stores information in two primary places: the short term memory and the long term memory. Everytime external stimuli are perceived and processed, they are initially stored as information in neural synapses. Synapses are the connections among brain cells, or neurons, where communication occurs by the release of neurotransmitters. Because the brain is constantly taking in sensory information during the day, its neurons are so busy communicating that they do not have time to sort through and encode the information. Diering and team were aware that only limited amounts of information could be retained in the short term memory before being lost for good. His study concluded that during sleep, the synapses involved in short term memory, especially those in the hippocampus and cortex areas, undergo a recalibration process which allows contained information to be correctly stored.

Diering and his research team gathered their data from the brains of live mice. Using a method of two-photon imaging and fluorescent dyes, they could tag proteins in mice synapses and track their activity under numerous experimental conditions. Two-photon imaging, also known as two-photon excitation microscopy, generates images by exciting fluorescently dyed molecules with laser beams of near-infrared light. The resulting wavelengths increase the depth of tissue that the microscope can view, producing an image. This method is ideal for imaging live cells because it minimizes the toxic effects caused by radiation.

Diering and team used fluorescent dyes to tag receptor proteins, the molecules responsible for receiving neurotransmitters for neural communication. Imaging showed that during sleep, mice brains underwent a 20% drop in receptor protein levels, which indicated uniform weakening of their synapses. During this weakening, the overall strength of the neural network remained intact, but communicative activity within each of the neurons would minimize alternatively, allowing for the learning and memory processing of information contained in synapses to be completed. Diering called this period of sorting through and encoding information homeostatic scaling down. Homeostatic scaling down gave mice brains the opportunity to move key information from the short term memory into the long term memory for more permanent retainment.

The homeostatic scaling down process is able to occur only during sleep due to a few factors. Firstly, sleep need is controlled by a neurotransmitter called adenosine. Secondly, at the onset of sleep, the levels of a neurotransmitter called noradrenaline significantly drop. Thirdly, the changes in protein receptor levels are driven by Homer1a, a gene important for the regulation of the sleep-wake cycle. Diering’s data shows there are noticeably higher concentrations of Homer1a in the synapses of sleeping mice than of waking mice, and that mice genetically deprived of Homer1a did not experience decreases in receptor protein numbers during sleep necessary for scaling down process to occur. He also found that when mice were administered an adenosine-blocking drug, Homer1a levels were not able to increase.

Based on this data, Diering was able to conclude that during the day, neurons accumulate Homer1a, but are not able to direct it to the synapses for information encoding to occur. When sleep is triggered by the release of adenosine, noradrenaline levels drop and Homer1a is able to enter synapses, thus causing the homeostatic scaling down process. This process weakens the receptor protein activity of synapses, and consequently their overall activity.  During this state of low activity, synapses are able to undergo memory and learning processes by creating contextual memories from sensory information. By transferring this information from the short term memory to long term memory, synapses can then remodel themselves for high activity during the next wake cycle.

Diering’s study demonstrates on a cellular level how vital sleep is for peak cognitive functioning during the day. In order to properly code and store memories, a process essential for new learning, the body must undergo enough time asleep for full synaptic calibration and remodeling to occur. Due to this, Diering found sleep deprivation to play a direct role in the interference of learning and memory because it prevents synapse remodeling and the homeostatic scaling down process. Though not yet tested, drugs such as benzodiazepines, sedatives, and muscle relaxants are hypothesized to disrupt similar sleep mechanisms, affecting learning and memory in similar ways because of the adenosine imbalances they cause in the brain.

Diering’s coauthors were Raja Nirujogi, Richard Roth, Paul Worley, Akhilesh Pandey, and Richard Huganir. The published study, “Homer1a drives homeostatic scaling-down of excitatory synapses during sleep,” can be found on the online journal Science.

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Posted by Kayla Klatt

Kayla is a freshman majoring in Molecular and Cellular Biology and minoring in Psychology. She is a premed student with aspirations of becoming a surgeon, and is currently persuing research oppurtnuites related to neurological studies. Kayla is a member of the varsity women's soccer team as well as a member of the Zeta Omicron chapter of Alpha Phi. She particpates in volunteer work through Alpha Phi such as fundraising for women's heart health and running non-profit community events. Kayla's goal as a member of HMR is to expose people to the biological and chemical bases that serve as the foundations for modern medical advancements.