biostudies-literatureHalassa MMNCCDPHP CDC HHSNIMH NIH HHSNINDS NIH HHSNIGMS NIH HHS808-821https://www.ebi.ac.uk/biostudies/studies/S-EPMC4205482biostudies-literatureUnknown158(4)Behavioral state is known to influence interactions between thalamus and cortex, which are important for sensation, action, and cognition. The thalamic reticular nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the underlying functional architecture of this process and its state dependence are unknown. By combining the first TRN ensemble recording with psychophysics and connectivity-based optogenetic tagging, we found reticular circuits to be composed of distinct subnetworks. While activity of limbic-projecting TRN neurons positively correlates with arousal, sensory-projecting neurons participate in spindles and show elevated synchrony by slow waves during sleep. Sensory-projecting neurons are suppressed by attentional states, demonstrating that their gating of thalamo-cortical interactions is matched to behavioral state. Bidirectional manipulation of attentional performance was achieved through subnetwork-specific optogenetic stimulation. Together, our findings provide evidence for differential inhibition of thalamic nuclei across brain states, where the TRN separately controls external sensory and internal limbic processing facilitating normal cognitive function. PAPERFLICK:CellState-dependent architecture of thalamic reticular subnetworks.PMC4205482R01 MH057414R25 MH094612R01MH101209TR01-GM10498R01 MH101209R01 GM104948DP1MH103908R01 MH061976R01-MH061976R00 NS078115K99 NS078115R01NS077986R01 NS077986DP1 MH103908R01MH057414K99 NS 078115Halassa MMZhao SChen ZWilson MAWang FWimmer RDZikopoulos BBrunetti PMBrown ENfalseState-dependent architecture of thalamic reticular subnetworks.Behavioral state is known to influence interactions between thalamus and cortex, which are important for sensation, action, and cognition. The thalamic reticular nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the underlying functional architecture of this process and its state dependence are unknown. By combining the first TRN ensemble recording with psychophysics and connectivity-based optogenetic tagging, we found reticular circuits to be composed of distinct subnetworks. While activity of limbic-projecting TRN neurons positively correlates with arousal, sensory-projecting neurons participate in spindles and show elevated synchrony by slow waves during sleep. Sensory-projecting neurons are suppressed by attentional states, demonstrating that their gating of thalamo-cortical interactions is matched to behavioral state. Bidirectional manipulation of attentional performance was achieved through subnetwork-specific optogenetic stimulation. Together, our findings provide evidence for differential inhibition of thalamic nuclei across brain states, where the TRN separately controls external sensory and internal limbic processing facilitating normal cognitive function. PAPERFLICK:2014-01-01T00:00:00Z2014 Aug2025-04-22T20:39:07.868Z2019-03-27T01:38:07ZS-EPMC42054822512678610.1016/j.cell.2014.06.025