Posts tagged sleep spindles
Articles and news from the latest research reports.
Scientists use lasers to control mouse brain switchboard
Ever wonder why it’s hard to focus after a bad night’s sleep? Using mice and flashes of light, scientists show that just a few nerve cells in the brain may control the switch between internal thoughts and external distractions. The study, partly funded by the National Institutes of Health, may be a breakthrough in understanding how a critical part of the brain, called the thalamic reticular nucleus (TRN), influences consciousness.
“Now we may have a handle on how this tiny part of the brain exerts tremendous control over our thoughts and perceptions,” said Michael Halassa, M.D., Ph.D., assistant professor at New York University’s Langone Medical Center and a lead investigator of the study. “These results may be a gateway into understanding the circuitry that underlies neuropsychiatric disorders.”
The TRN is a thin layer of nerve cells on the surface of the thalamus, a center located deep inside the brain that relays information from the body to the cerebral cortex. The cortex is the outer, multi-folded layer of the brain that controls numerous functions, including one’s thoughts, movements, language, emotions, memories, and visual perceptions. TRN cells are thought to act as switchboard operators that control the flow of information relayed from the thalamus to the cortex.
“The future of brain research is in studying circuits that are critical for brain health and these results may take us a step further,” said James Gnadt, Ph.D., program director at NIH’s National Institute Neurological Disorders and Stroke (NINDS), which helped fund the study. “Understanding brain circuits at the level of detail attained in this study is a goal of the President’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.”
To study the circuits, the researchers identified TRN cells that send inhibitory signals to parts of the thalamus known to relay visual information to the cortex. Using a technique known as multi-electrode recordings, they showed that sleep and concentration affected these cells in opposite ways.
They fired often when the mice were asleep, especially during short bursts of simultaneous brain cell activity called sleep spindles. These activity bursts briefly widen electrical brain wave traces making them look like spindles, the straight spikes with rounded bottoms used to make yarn. In contrast, the cells fired infrequently when the mice were tasked with using visual cues to find food. The results suggested that these cells blocked visual information from reaching the cortex during sleep and allowed its transmission when the mice were awake and attentive.
For Dr. Halassa, a practicing psychiatrist who treats schizophrenia, these surprising results may provide fundamental insights into how the brain controls information transmission, a process that is disrupted in patients with neuropsychiatric disorders. Previous studies suggested that people who experienced more spindles while sleeping were less susceptible to being disturbed by outside noises. Moreover, people with schizophrenia and autism spectrum disorder may experience fewer spindles.
“Spindles may be peepholes into the mysteries of these disorders,” said Dr. Halassa.
To test this idea, the researchers used optogenetics, a technique that introduces light-sensitive molecules into nerve cells. This allowed them to precisely control the firing patterns of visual TRN cells with flashes of laser light. The experiments were performed in well-rested as well as sleep-deprived mice. Similar to what is seen in humans, sleep deprivation can disrupt the ability of mice to focus and block out external distractions.
Well-rested mice needed just a second or two to find the food whereas sleep-deprived mice took longer, suggesting that lack of sleep had detrimental effects on their ability to focus. When the researchers used flashes of laser light to inhibit the firing of optogenetically engineered visual TRN cells in sleep-deprived mice, the mice found the food faster. In contrast, if they used optogenetics to induce sleep-like firing patterns in well-rested mice, then the mice took longer to find food.
“It’s as if with a flick of a switch we could alter the mental states of the mice and either mimic or cure their drowsiness,” said Dr. Halassa.
In a parallel set of experiments the researchers found neighbors of the visual TRN cells had very different characteristics. These neighboring cells control the flow of information to the cortex from limbic brain regions, which are involved with memory formation, emotions and arousal. The cells fired very little during sleep and instead were active when the mice were awake. Dr. Halassa thinks that their firing pattern may be important for the strengthening of new memories that often occurs during sleep. Combined, the results suggest that the TRN is divided into sub-networks that oversee discrete mental states. The researchers think understanding the sub-networks is an initial step in thoroughly exploring the role of the TRN in brain disorders.
Sleep Mechanism Identified That Plays Role in Emotional Memory
Sleep researchers from University of California campuses in Riverside and San Diego have identified the sleep mechanism that enables the brain to consolidate emotional memory and found that a popular prescription sleep aid heightens the recollection of and response to negative memories.
Their findings have implications for individuals suffering from insomnia related to posttraumatic stress disorder (PTSD) and other anxiety disorders who are prescribed zolpidem (Ambien) to help them sleep.
The study — “Pharmacologically Increasing Sleep Spindles Enhances Recognition for Negative and High-arousal Memories” — appears in the Journal of Cognitive Neuroscience. It was funded by a National Institutes of Health career award to Sara C. Mednick, assistant professor of psychology at UC Riverside, of $651,999 over five years.
Mednick and UC San Diego psychologists Erik J. Kaestner and John T. Wixted determined that a sleep feature known as sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — are important for emotional memory.
Research Mednick published earlier this year demonstrated the critical role that sleep spindles play in consolidating information from short-term to long-term memory in the hippocampus, located in the cerebral cortex of the brain. Zolpidem enhanced the process, a discovery that could lead to new sleep therapies to improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia. It was the first study to show that sleep can be manipulated with pharmacology to improve memory.
“We know that sleep spindles are involved in declarative memory — explicit information we recall about the world, such as places, people and events, ” she explained.
But until now, researchers had not considered sleep spindles as playing a role in emotional memory , focusing instead on rapid eye movement (REM) sleep.
Using two commonly prescribed sleep aids — zolpidem and sodium oxybate (Xyrem) — Mednick, Kaestner and Wixted were able to tease apart the effects of sleep spindles and rapid eye movement (REM) sleep on the recall of emotional memories. They determined that sleep spindles, not REM, affect emotional memory.
The researchers gave zolpidem, sodium oxybate (Xyrem) and a placebo to 28 men and women between the ages of 18 and 39 who were normal sleepers, allowing several days between doses to allow the pharmaceuticals to leave their bodies. The participants viewed standardized images known to elicit positive and negative responses for one second before and after taking supervised naps. They recalled more images that had negative or highly arousing content after taking zolpidem, a finding that also suggests that the brain may favor consolidation of negative memories, she said.
“I was surprised by the specificity of the results, that the emotional memory improvement was specifically for the negative and high-arousal memories, and the ramifications of these results for people with anxiety disorders and PTSD,” Mednick said. “These are people who already have heightened memory for negative and high-arousal memories. Sleep drugs might be improving their memories for things they don’t want to remember.”
The study may have even broader implications, the researchers said. Clinical guidelines of the U.S. Department of Veterans Affairs and Department of Defense recommend against the routine use of benzodiazepines to treat PTSD, although their use increased among men and women with PTSD between 2003 and 2010. The effects of benzodiazepines on sleep are similar to those of zolpidem.
The U.S. Air Force uses zolpidem as one of the prescribed “no-go pills” to help flight crews calm down after taking stimulants to stay awake during long missions, the researchers noted in the study.
“In light of the present results, it would be worthwhile to investigate whether the administration of benzodiazepine-like drugs may be increasing the retention of highly arousing and negative memories, which would have a countertherapeutic effect,” they wrote. “Further research on the relationship between hypnotics and emotional mood disorders would seem to be in order.”
(Source: ucrtoday.ucr.edu)