August 16, 2014
With The Flick Of A ‘Switch’ Researchers Alter Mental Status Of Mice
April Flowers for redOrbit.com - Your Universe Online
Last night you couldn't get to sleep until the wee hours, and today you can't seem to concentrate on anything. You know the two are related, but how? A new study led by NYU Langone Medical Center and funded by the National Institutes of Health (NIH) has found that just a few nerve cells in the brain may control the switch between internal thoughts and external distractions. The findings, published in Cell, may represent a breakthrough in understanding how the thalamic reticular nucleus (TRN) – a vital part of the brain — 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. "These results may be a gateway into understanding the circuitry that underlies neuropsychiatric disorders."
"We have never been able to observe as precisely how this structure worked before,” Halassa added.
The thalamus is a structure deep inside the brain that relays information from the body to the cerebral cortex. The TRN is a thin layer of nerves on the surface of this structure. The cerebral cortex is the outer, multi-folded layer of the brain. The cortex controls many functions, including thoughts, movement, language, emotions, memories and visual perceptions. Scientists believe that the TRN nerves act as a switchboard, controlling the flow of information between the thalamus and the cortex.
Dr. Halassa and his team studied the firing patterns of TRN cells in mice, during both sleep and arousal, to understand how the switchboard might work. Sleep and arousal are two very different states of consciousness, with very different processing needs. The team found that TRN has many “switchboard operators,” and that each controls a specific line of communication between the two brain structures. They used this information to learn to control the attention span in mice.
"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). "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."
First, the team identified TRN cells that send inhibitory signals to parts of the thalamus known to relay visual information to the cerebral cortex. Then, the researchers used multi-electrode recordings to show that sleep and concentration affect these cells in opposite ways.
When the mice were asleep, these TRN cells fired often. This was especially true during bursts of simultaneous brain cell activity called sleep spindles. During these activity bursts, brain wave traces are briefly widened, making them look like yarn spindles — straight spikes with rounded bottoms. When the mice were tasked with using visual cues to find food, however, the cells fired very infrequently, suggesting that the cells blocked visual information from reaching the cortex during sleep and allowed the information to transmit when the mice were awake and attentive.
These findings, according to Halassa, might provide fundamental insights into how the brain controls information transmission. Halassa, who is a practicing psychiatrist treating patients with schizophrenia, says this is important because information transmission is interrupted in patients with neuropsychiatric disorders. People who experience more spindles during sleep are less likely to be disturbed by outside noises, according to prior studies. It has also been noted that people with schizophrenia and autism experience fewer spindles.
[ Watch: Exploring A Brain’s Switchboard Operators ]
"Spindles may be peepholes into the mysteries of these disorders," said Dr. Halassa.
The researchers used optogenetics, which introduces light-sensitive molecules into nerve cells, to precisely control the firing patterns of visual TRN cells with flashes of laser light. The team performed the experiment with both well-rested and sleep-deprived mice. It has been noted in the past that sleep-deprivation in mice can disrupt the ability to focus and block out distractions.
They found that well-rested mice needed only seconds to find the food. Sleep-deprived mice, however, took longer, indicating that lack of sleep has a detrimental effect on the ability to focus. Flashes of laser light were used to inhibit the firing of optogenetically engineered TRN cells in sleep-deprived mice. This allowed them to find the food faster. The reverse was also true, firing flashes of laser light to induce sleep-like firing patterns in the well-rested mice made it harder for the mice to find food.
"With a flick of a light switch, we seemed able to alter the mental status of the mice, changing the speed at which information can travel in the brain," says Dr. Halassa.
The researchers also found that the cells near the visual TRN cells had very different characteristics. Instead of visual information, these cells control the flow of information from the limbic brain regions (known to control memory formation, emotions and arousal) to the cerebral cortex. They found that during sleep, these cells fired very infrequently. Instead, they were very active while the mice were awake, suggesting that their firing pattern is important for the strengthening of new memories which occurs during sleep. Halassa says the combined results suggest that the TRN is divided into sub-networks. Each of these sub-networks oversees discrete mental states, and understanding how they operate could be an initial step in exploring the role of the TRN in brain disorders.