Scientists showed that they could alter brain activity of rats and
either wake them up or put them in an unconscious state by changing the
firing rates of neurons in the central thalamus, a region known to
regulate arousal. The study, published in eLIFE, was partially funded by
the National Institutes of Health.
“Our results suggest the central thalamus works like a radio dial
that tunes the brain to different states of activity and arousal,” said
Jin Hyung Lee, Ph.D., assistant professor of neurology, neurosurgery and
bioengineering at Stanford University, and a senior author of the
Located deep inside the brain the thalamus acts as a relay station
sending neural signals from the body to the cortex. Damage to neurons in
the central part of the thalamus may lead to problems with sleep,
attention, and memory. Previous studies suggested that stimulation of
thalamic neurons may awaken patients who have suffered a traumatic brain
injury from minimally conscious states.
Dr. Lee’s team flashed laser pulses onto light sensitive central
thalamic neurons of sleeping rats, which caused the cells to fire. High
frequency stimulation of 40 or 100 pulses per second woke the rats. In
contrast, low frequency stimulation of 10 pulses per second sent the
rats into a state reminiscent of absence seizures that caused them to
stiffen and stare before returning to sleep.
“This study takes a big step towards understanding the brain
circuitry that controls sleep and arousal,” Yejun (Janet) He, Ph.D.,
program director at NIH’s National Institute of Neurological Disorders
and Stroke (NINDS).
When the scientists used functional magnetic resonance imaging (fMRI)
to scan brain activity, they saw that high and low frequency
stimulation put the rats in completely different states of activity.
Cortical brain areas where activity was elevated during high frequency
stimulation became inhibited with low frequency stimulation. Electrical
recordings confirmed the results. Neurons in the somatosensory cortex
fired more during high frequency stimulation of the central thalamus and
less during low frequency stimulation.
“Dr. Lee’s innovative work demonstrates the power of using imaging
technologies to study the brain at work,” said Guoying Liu, Ph.D., a
program director at the NIH’s National Institute of Biomedical Imaging
and Bioengineering (NIBIB).
How can changing the firing rate of the same neurons in one region lead to different effects on the rest of the brain?
Further experiments suggested the different effects may be due to a
unique firing pattern by inhibitory neurons in a neighboring brain
region, the zona incerta, during low frequency stimulation.
Cells in this brain region have been shown to send inhibitory signals to
cells in the sensory cortex.
Electrical recordings showed that during low frequency stimulation of the central thalamus, zona incerta
neurons fired in a spindle pattern that often occurs during sleep. In
contrast, sleep spindles did not occur during high frequency
stimulation. Moreover, when the scientists blocked the firing of the zona incerta neurons during low frequency stimulation of the central thalamus, the average activity of sensory cortex cells increased.
Although deep brain stimulation of the thalamus has shown promise as a
treatment for traumatic brain injury, patients who have decreased
levels of consciousness show slow progress through these treatments.
“We showed how the circuits of the brain can regulate arousal
states,” said Dr. Lee. “We hope to use this knowledge to develop better
treatments for brain injuries and other neurological disorders.”
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