Astrocytes modulate neuronal activity by releasing chemical transmitters via a process termed gliotransmission. The role of this process in the control of behavior is unknown. Since one outcome of SNARE-dependent gliotransmission is the regulation of extracellular adenosine and because adenosine promotes sleep, we genetically inhibited the release of gliotransmitters and asked if astrocytes play an unsuspected role in sleep regulation. Inhibiting gliotransmission attenuated the accumulation of sleep pressure, assessed by measuring the slow wave activity of the EEG during NREM sleep and prevented cognitive deficits associated with sleep loss. Since the sleep-suppressing effects of the A1 receptor antagonist CPT were prevented following inhibition of gliotransmission and because intracerebroventricular delivery of CPT to wildtype mice mimicked the transgenic phenotype we conclude that astrocytes modulate the accumulation of sleep pressure and its cognitive consequences through a pathway involving A1 receptors.

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While interactions between the thalamus and cortex are critical for cognitive function1–3, the exact contribution of the thalamus to these interactions is often unclear. Recent studies have shown diverse connectivity patterns across the thalamus 4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here, by investigating prefrontal cortical (PFC) representation of two rules used to guide attention, we find that the mediodorsal thalamus (MD) sustains these representations without relaying categorical information. Specifically, MD input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioral performance, while enhancing MD excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function indicates that the thalamus plays much more central roles in cognition than previously thought.