By flashing high-frequency (40 to 100 pulses per second) optogenetic lasers at the brain’s thalamus, scientists were able to wake up sleeping rats and cause widespread brain activity. In contrast, flashing the laser at 10 pulses per second suppressed the activity of the brain’s sensory cortex and caused rats to enter a seizure-like state of unconsciousness.
“We hope to use this knowledge to develop better treatments for brain injuries and other neurological disorders,” said Jin Hyung Lee, Ph.D., assistant professor of neurology, neurosurgery, and bioengineering at Stanford University, and a senior author of the study, published in the open-access journal eLIFE.
Ref: Frequency-selective control of cortical and subcortical networks by central thalamus. eLife (10 December 2015) | DOI: 10.7554/eLife.09215
Central thalamus plays a critical role in forebrain arousal and organized behavior. However, network-level mechanisms that link its activity to brain state remain enigmatic. Here, we combined optogenetics, fMRI, electrophysiology, and video-EEG monitoring to characterize the central thalamus-driven global brain networks responsible for switching brain state. 40 and 100 Hz stimulations of central thalamus caused widespread activation of forebrain, including frontal cortex, sensorimotor cortex, and striatum, and transitioned the brain to a state of arousal in asleep rats. In contrast, 10 Hz stimulation evoked significantly less activation of forebrain, inhibition of sensory cortex, and behavioral arrest. To investigate possible mechanisms underlying the frequency-dependent cortical inhibition, we performed recordings in zona incerta, where 10, but not 40, Hz stimulation evoked spindle-like oscillations. Importantly, suppressing incertal activity during 10 Hz central thalamus stimulation reduced the evoked cortical inhibition. These findings identify key brain-wide dynamics underlying central thalamus arousal regulation.