The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, is known to regulate thalamocortical interactions critical for sensory processing, attention and cognition
1
-
5
. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders
6
-
9
. Currently, little is known about the organizational principles underlying its divergent functions. We performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that TRN cellular heterogeneity is characterized by a transcriptomic gradient of two negatively correlated gene expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core/shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections to the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN-thalamus subnetworks. Selective perturbation of the two subnetworks
in vivo
revealed their differential role in regulating sleep. Taken together, our study provides a comprehensive atlas for TRN neurons at the single-cell resolution, and links molecularly defined subnetworks to the functional organization of the thalamo-cortical circuits.
High-density electroencephalographic (hdEEG) recordings are widely used in human studies to determine spatio-temporal patterns of cortical electrical activity. How these patterns of activity are modulated by subcortical arousal systems is poorly understood. Here, we couple selective optogenetic stimulation of a defined subcortical cell-type, basal forebrain (BF) parvalbumin (PV) neurons, with hdEEG recordings in mice (Opto-hdEEG). Stimulation of BF PV projection neurons preferentially generated time-locked gamma oscillations in frontal cortices. BF PV gammafrequency stimulation potently modulated an auditory sensory paradigm used to probe cortical function in neuropsychiatric disorders, the auditory steady-state response (ASSR). Phase-locked excitation of BF PV neurons in advance of 40 Hz auditory stimuli enhanced the power, precision and reliability of cortical responses, and the relationship between responses in frontal and auditory cortices. Furthermore, synchronization within a frontal hub and long-range cortical interactions
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.