Scientists Probe Role of Sleep in Memory
Sleep Deprivation: Timing Is Everything
Previous studies show even brief stretches of sleep loss impair hippocampal function. Press conference presenter Ted Abel and colleagues at the University of Pennsylvania investigated just how little sleep loss it takes to jeopardize memory consolidation by depriving mice of sleep for varying lengths and periods of time after they learned a new task. Abel and his colleagues found that preventing mice from sleeping for three hours, two to five hours after training impaired the ability of the mice to perform the task the next day. However, when the researchers shifted the deprivation period to just one hour earlier, the mice properly stored the memory and recalled it the next day.
Between two and four hours after training, “something is happening normally during sleep that’s particularly vulnerable to deprivation,” said Abel. According to Abel, the data suggest that memories are reactivated during this time window.
Sleeplessness Disrupts Connectivity
Sleep deprivation also alters the connections between some regions of the brain, according to press conference presenter Hengyi Rao, also of the University of Pennsylvania. Rao described his recent imaging work examining how sleep deprivation affects the connections between the hippocampus and the brain’s default mode network (DMN) — a group of regions hard at work when the brain is awake but not engaged in a mental task.
Rao and colleagues performed a functional MRI (fMRI) on 22 healthy adults after a full night’s sleep (nine hours), after 24 hours without sleep, and once more after two nights of recovery sleep (20 hours total). According to Rao, while sleep deprivation did not alter the activity of the DMN, hippocampal communication with the DMN “disappeared” after 24 hours of sleep deprivation, but was restored to normal levels after sleep recovery.
According to Rao, decreased connectivity between the DMN and hippocampus was associated with poor performance on a memory task — the less hippocampal connectivity, the less the participant was able to recall. The loss of its connection with the DMN suggests the importance of hippocampal function to memory at rest as well as during active memory formation, Rao said.
Sleepiness Throws Default Network Out of Sync
Previous imaging studies show that the disparate brain areas of the DMN have similar activity patterns during rest, but certain conditions can cause these patterns to fall out of sync. The coherence of activity patterns from different regions in the network can tell researchers how well the network is functioning as a whole.
Decreases in DMN coherence have been associated with increased daytime sleepiness, decline in memory, and early symptoms of Alzheimer’s disease. Elderly people without memory problems also report sleep problems, including increased daytime sleepiness. However, the relationship between chronic daytime sleepiness in healthy elderly people and DMN connectivity has not been studied. Press conference presenter Andrew Ward, a postdoctoral fellow working in the laboratory of Reisa Sperling at Massachusetts General Hospital, examined whether reports of daytime sleepiness by elderly adults without memory problems correlated with decreased DMN coherence.
Ward and colleagues asked 84 healthy older adults to report how likely they were to fall asleep during daily activities, ranging from watching TV in the dark to driving, before they underwent a resting-state functional connectivity MRI (fcMRI). Those who reported the least daytime sleepiness displayed the healthiest DMN activity, whereas sleepy participants showed a less coordinated DMN.
The results suggest that “brain function is going down with sleepiness before there are reports of memory problems,” Ward said during the press conference. Ward noted that efforts to improve the amount of sleep people receive at night may be able to improve DMN connectivity and decrease the risk of developing Alzheimer’s disease.
Sleep Helps Brain to Forget
Previous research shows sleep plays an important role in memory formation and storage, but scientists are continuing to work to understand just how sleep alters memories. Several press conference presenters discussed evidence suggesting sleep helps make way for new information by clearing out old associations.
“We learn mostly by strengthening [synaptic] connections, but that strengthening has consequences,” explained Giulio Tononi, of the University of Wisconsin, Madison. Extraneous synapses make neurons more “expensive”: they occupy valuable real estate and cost precious resources to maintain, he noted. In addition, they compromise our ability to learn from new experiences.
Tononi described a growing body of evidence that supports the hypothesis that during sleep synaptic strength is globally reduced to a baseline level that is energetically sustainable and beneficial for memory and performance. Recent studies suggest that after sleep there are fewer synapses; they are smaller; less electrically active; and they have fewer glutamate receptors.
One mechanism that may contribute to the weakening of synapses within the memory network during sleep is the reduction of the neurotransmitter noradrenaline (NA), according to press conference presenter Gina Poe of the University of Michigan.
Previous studies show NA is absent during rapid eye movement (REM) sleep and the seconds preceding sleep spindle waves during non-REM sleep. Poe and colleagues examined what would happen if they prevented the drop in NA during sleep.
They delivered an antidepressant drug that maintains synaptic NA or infused NA directly to the hippocampus in sleeping rats after the rats learned a task. They then recorded memory circuit activity while the animal slept or learned a new environment.
Behavioral tests indicated that when the rats did not experience the drop in NA during post-learning sleep, new information could not be consolidated with old. Such findings could one day guide new treatments for post-traumatic stress disorder (PTSD), where research suggests NA levels remain elevated during sleep and the forgetting process that accompanies sleep appears to be impaired, keeping the traumatic experience fresh.
Manipulating Memories During Sleep
Some people with PTSD benefit from extinction therapy, in which a traumatic memory is repeatedly re-experienced in a safe setting. However, reliving painful memories can be emotionally difficult and, because memory is context-dependent, it may succeed in a therapist’s office only to fail in real life. Could manipulation of memories during sleep provide a more effective therapy?
Press conference presenter Asya Rolls, working in the labs of H. Craig Heller and Luis de Lecea at Stanford University, conditioned mice to fear the scent of jasmine by pairing the odor with a foot shock. Later, when the mice were sleeping, the researchers released puffs of the jasmine scent, reactivating the fear memory. Mice exposed to the odor during sleep demonstrated a greater fear response upon waking, suggesting the fear memory was strengthened during sleep.
The researchers found that if they delivered a protein synthesis inhibitor in the amygdala before the trained mice slept, the fear memory was extinguished upon waking. The model provides a proof-of-concept that memories can be manipulated during sleep.
Together, this research hints at how sleep may provide an important time for the brain to get organized for memory — filing away important memories and disposing of unnecessary associations — following a day’s events. Scientists are hopeful advances in imaging and other technology will one day lead to new answers about sleep and memory, as well as viable new treatments for Alzheimer’s disease and PTSD, conditions where sleep processes are particularly vulnerable.
