Frequency-selective control of cortical and subcortical networks by central thalamus
Jia Liu,
Hyun Joo Lee,
Andrew J Weitz,
Zhongnan Fang,
Peter Lin,
ManKin Choy,
Robert Fisher,
Vadim Pinskiy,
Alexander Tolpygo,
Partha Mitra,
Nicholas Schiff,
Jin Hyung Lee
Affiliations
Jia Liu
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States
Hyun Joo Lee
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States
Andrew J Weitz
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States; Department of Bioengineering, Stanford University, Stanford, United States
Zhongnan Fang
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States; Department of Electrical Engineering, Stanford University, Stanford, United States
Peter Lin
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States
ManKin Choy
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States
Robert Fisher
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States
Vadim Pinskiy
Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
Alexander Tolpygo
Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
Partha Mitra
Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
Nicholas Schiff
Department of Neurology, Weill Cornell Medical College, New York, United States
Jin Hyung Lee
Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States; Department of Bioengineering, Stanford University, Stanford, United States; Department of Electrical Engineering, Stanford University, Stanford, United States; Department of Neurosurgery, Stanford University, Stanford, United States
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.
