We screened for novel circuits in the mouse brain that promote wakefulness. Chemogenetic activation experiments and EEG recordings pointed to glutamatergic/nitrergic (NOS1) and GABAergic neurons in the VTA. Activating glutamatergic/NOS1 neurons, which were wake- and REM-sleep-active, produced wakefulness through projections to the nucleus accumbens and the lateral hypothalamus. Lesioning the glutamate cells impaired the consolidation of wakefulness. By contrast, activation of GABAergic VTA neurons elicited long-lasting NREM-like sleep resembling sedation. Lesioning these neurons produced an increase in wakefulness that persisted for at least 4 months. Surprisingly, these VTA GABAergic neurons were wake-and REM-sleep-active. We suggest that GABAergic VTA neurons may limit wakefulness by inhibiting the arousal-promoting VTA glutamatergic and/or dopaminergic neurons and through projections to the lateral hypothalamus. Thus, in addition to its contribution to goal- and reward-directed behaviours, the VTA has a role in regulating sleep and wakefulness.

The management of severe neurologic infections due to multidrug-resistant (MDR) Klebsiella pneumoniae infection remains a challenge. Limited antibiotic treatment regimens make treatment of severe MDR K. pneumoniae infection more difficult. We describe a patient who developed severe meningitis and ventriculitis after craniotomy caused by MDR K. pneumoniae and was effectively treated with the administration of multichannel applications (intravenous, intrathecal and aerosol inhalation) of colistin sulfate. This case provides clinical evidence that the intrathecal, intravenous and aerosol inhalation of colistin sulfate by multichannel application can be a last resort in refractory intracranial infection by MDR K. pneumoniae.