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State-dependent architecture of thalamic reticular subnetworks.

ABSTRACT: 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:

SUBMITTER: Halassa MM

PROVIDER: S-EPMC4205482 | biostudies-other | 2014 Aug

REPOSITORIES: biostudies-other

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Project description:Spike-and-wave discharges and an accompanying loss of consciousness are hallmarks of absence seizure, which is a childhood generalized epilepsy disorder. In absence seizure, dysfunction of the cortico-thalamo-cortico circuitry is thought to engage in abnormal cortical rhythms. Previous studies demonstrated that the thalamic reticular nucleus has a critical role in the formation of normal cortical rhythms; however, whether thalamic reticular nucleus dysfunction leads directly to abnormal rhythms, such as epilepsy, is largely unknown. We found that expressing the inhibitory opsin, archaerhodopsin, including in the thalamic reticular nucleus, caused abnormal cortical rhythms in Pvalb-tetracycline transactivator::tetO-ArchT (PV-ArchT) double transgenic mice. We validated the PV-ArchT line as a new mouse model of absence seizure through physiological and pharmacological analyses, as well as through examining their behavioural features. We then discovered that archaerhodopsin expression exclusively in thalamic reticular nucleus parvalbumin-positive neurons was sufficient to induce cortical spike-and-wave discharges using adeno-associated virus-mediated thalamic reticular nucleus targeting. Furthermore, we found that archaerhodopsin expression impaired rebound burst firing and T-current in thalamic reticular nucleus parvalbumin-positive cells by slice physiology. Although T-current in the thalamic reticular nucleus was impaired, the T-current blocker ethosuximide still had a therapeutic effect in PV-ArchT mice, suggesting a gain of function of T-type calcium channels in this absence seizure model. However, we did not find any over- or misexpression of T-type calcium channel genes in the thalamus or the cortex. Thus, we demonstrated that thalamic reticular nucleus dysfunction led to an absence seizure-like phenotype in mice. In a final set of experiments, we showed that the archaerhodopsin-mediated absence seizure-like phenotype disappeared after the removal of archaerhodopsin by using a time-controllable transgenic system. These data may provide a hint as to why many absence seizures naturally regress.

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State-dependent architecture of thalamic reticular subnetworks.

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