Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness.

During non-rapid eye movement (NREM) sleep, synchronous synaptic activity in the thalamocortical network generates predominantly low-frequency oscillations (<4 Hz) that are modulated by inhibitory inputs from the thalamic reticular nucleus (TRN). Whether TRN cells integrate sleep-wake signals from subcortical circuits remains unclear. We found that GABA neurons from the lateral hypothalamus (LHGABA) exert a strong inhibitory control over TRN GABA neurons (TRNGABA). We found that optogenetic activation of this circuit recapitulated state-dependent changes of TRN neuron activity in behaving mice and induced rapid arousal during NREM, but not REM, sleep. During deep anesthesia, activation of this circuit induced sustained cortical arousal. In contrast, optogenetic silencing of LHGABA-TRNGABA transmission increased the duration of NREM sleep and amplitude of delta (1-4 Hz) oscillations. Collectively, these results demonstrate that TRN cells integrate subcortical arousal inputs selectively during NREM sleep and may participate in sleep intensity

Connections between the zona incerta and superior colliculus in the monkey and squirrel

The zona incerta contains GABAergic neurons that project to the superior colliculus in the cat and rat, suggesting that it plays a role in gaze changes. However, whether this incertal connection represents a general mammalian pattern remains to be determined. We used neuronal tracers to examine the zona incerta connections with the midbrain tectum in the gray squirrel and macaque monkey. Collicular injections in both species revealed that most incertotectal neurons lay in the ventral layer, but anterogradely labeled tectoincertal terminals were found in both the dorsal and ventral layers. In the monkey, injections of the pretectum also produced retrograde labeling, but mainly in the dorsal layer. The dendritic fields of incertotectal and incertopretectal cells were generally contained within the layer inhabited by their somata. The macaque, but not the squirrel, zona incerta extended dorsolaterally, within the external medullary lamina. Zona incerta injections produced retrogradely labeled neurons in the superior colliculus of both species. In the squirrel, most cells inhabited the lower sublamina of the intermediate gray layer, but in the monkey, they were scattered throughout the deeper layers. Labeled cells were present among the pretectal nuclei in both species. Labeled terminals were concentrated in the lower sublamina of the intermediate gray layer of both species, but were dispersed among the pretectal nuclei. In summary, an incertal projection that is concentrated on the collicular motor output layers and that originates in the ventral layer of the ipsilateral zona incerta is a common mammalian feature, suggesting an important role in collicular function