Minding the Pulse of Memory Consolidation

Thalamus (red)WIKIMEDIA, LIFE SCIENCE DATABASESSleep is essential for memory. Mounting evidence continues to support the notion that the nocturnal brain replays, stabilizes, reorganizes, and strengthens memories while the body is at rest. Recently, one particular facet of this process has piqued the interest of a growing group of neuroscientists: sleep spindles. For years these brief bursts of brain activity have been largely ignored. Now it seems that examining these neuronal pulses could help researchers better understand—perhaps even treat—cognitive impairments. Sleep spindles are a defining characteristic of stage 2 non-rapid eye movement (NREM) sleep. These electrical bursts between 10-16 Hz last only around a second, and are known to occur in the human brain thousands of times per night. Generated by a thin net of neurons enveloping the thalamus, spindles appear across several regions of the brain, and are thought to perform various functions, including maintaining sleep in the face of disturbances in the environment. It appears they are also a fundamental part of the process by which the human brain consolidates memories during sleep. A memory formed during the day is stored temporarily in the hippocampus, before being spontaneously replayed during the night. Information about the memory is distributed out and integrated into the neocortex through an orchestra of slow-waves, spindles, and rapid hippocampal ripples. Spindles, it seems, could be a guiding force—providing the plasticity and coordination needed for this delicate, interregional transfer of information. “Spindles appear to play a central role whenever memories during sleep are undergoing transformation that might be necessary to integrate them into neocortical long-term storage networks,” Jan Born, a professor of behavioral neurobiology of the University of Tübingen, told The Scientist during a conference dedicated to sleep spindles held in Budapest in May. Fewer spindles, therefore, would be expected to coincide with a breakdown in memory consolidation. People with schizophrenia show problems with sleep and memory consolidation. In a 2015 Biological Psychiatry review, researchers highlighted a paucity of spindles in many schizophrenic patients. “We believe that the deficit of spindle density in schizophrenia impairs sleep-dependent memory consolidation,” review coauthor Dara Manoach, a neuropsychologist at the Massachusetts General Hospital, wrote in an email. Surveying the literature, Manoach and colleagues also found that this deficit is associated with genetic risk for schizophrenia; the researchers proposed that spindles could be used as a hereditary biomarker to indicate memory consolidation–related and other issues during sleep. “It seems like a robust finding,” said Michael Halassa, an assistant professor of psychiatry at the New York University’s Langone Medical Center, who was not involved in the work. “The deficit in spindles could really reflect a larger deficit in overall regulation of thalamic function.” Meanwhile, another group—led by neuroscientist György Buzsáki of Langone Medical Center—recently found aberrant spindles revealing faults in the memory-consolidation systems of people with epilepsy. Buzsáki’s team found that interictal epileptiform discharges (IEDs)—short, abnormal patterns between seizures normally originating in the hippocampus—were appropriating the memory consolidation system in both mice and humans, tricking the brain into firing random patterns of electricity and creating spindles. The discharge “hijacks the three pillars of memory consolidation,” Buzsaki said at the Budapest conference, referring to the interchange between slow waves, spindles, and ripples. The group’s results were published in Nature Medicine in April. This nonsense firing is believed to affect cognitive impairments that hinder epileptic patients, too. “The paradox here is that while spindles are considered as a good thing for memory consolidation, we show that IED triggered spindles are bad,” Buzsáki noted in a follow-up email. “[This] shows the mechanistic deficit underlying decreased memory consolidation in epilepsy,” Liza Genzel of the University of Edinburgh’s Centre for Cognitive and Neural Systems, who was not involved in the study, wrote in an email to The Scientist. Some groups have hypothesized that boosting spindles might be useful for improving memory performance. Using transcranial alternating current stimulation (tACS), a weak electrical stimulation applied to the scalp, Flavio Frohlich of the University of North Carolina, Chapel Hill, and colleagues created a feedback system wherein a detected spindle would be followed by an artificial stimulation in the same frequency range, boosting the following spindle. The results of this 16-person study, published today (July 28) in Current Biology, found that motor memory performance increased following a night’s sleep with this tACS-based treatment. “This demonstrated a direct causal link between the electric activity pattern of sleep spindles and the process of motor memory consolidation,” said Frohlich. Joel Voss of the Northwestern University Feinberg School of Medicine, who was not involved in the study, is skeptical. “While the question of sleep spindles and memory consolidation is very important, I can’t tell what this study adds because the effects of stimulation were so weak,” he noted in an email to The Scientist. “Obviously these findings will have to be replicated, but they hold great potential promise for better understanding the role of sleep and memory and might even open new avenues for diagnostics and therapies,” said neurologist Kaspar Schindler of the University of Bern who also was not involved in the study. While they have been historically understudied, sleep spindles are among the first recognizable patterns produced by the cortex, noted Buzsáki. “This alone means that it’s worthwhile to study them.” C. Lustenberger et al., “Feedback-controlled transcranial alternating current stimulation reveals a functional role of sleep spindles in motor memory consolidation,” Current Biology, doi:10.1016/j.cub.2016.06.044, 2016.

Minding the Pulse of Memory Consolidation

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