The Journal of neuroscience : the official journal of the Society for Neuroscience
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The sleep-promoting ventrolateral preoptic nucleus (VLPO) shares reciprocal inhibitory inputs with wake-active neuronal nuclei, including the locus ceruleus. Electrophysiologically, sleep-promoting neurons in the VLPO are directly depolarized by the general anesthetic isoflurane and hyperpolarized by norepinephrine, a wake-promoting neurotransmitter. However, the integration of these competing influences on the VLPO, a sleep- and anesthetic-active structure, has yet to be evaluated in either brain slices in vitro or the intact organism. ⋯ Indeed, both norepinephrine and the highly selective α2 agonist dexmedetomidine each reversed the VLPO depolarization induced by isoflurane in slices in vitro. When microinjected directly into the VLPO of a mouse lightly anesthetized with isoflurane, dexmedetomidine increased behavioral arousal and reduced the depressant effects of isoflurane on barrel cortex somatosensory-evoked potentials but failed to elicit spectral changes in spontaneous EEG. Based on these observations, we conclude that local modulation of α-adrenergic activity in the VLPO destabilizes, but does not fully antagonize, the anesthetic state, thus priming the brain for anesthetic emergence.
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The lateral habenula (LHb) regulates the activity of monoaminergic neurons in the brainstem. This area has recently attracted a surge of interest in psychiatry because studies have reported the pathological activation of the habenula in patients with major depression and in animal models. The LHb plays a significant role in the pathophysiology of depression; however, how habenular neurons are activated to cause various depression symptoms, such as reduced motivation and sleep disturbance, remain unclear. ⋯ These animals also displayed increased susceptibility to chronic stress, displaying more frequent avoidant behavior without affecting locomotor activity in the open-field test. Intriguingly, the mice showed disinhibition of rapid eye movement sleep, which is a characteristic sleep pattern in patients with depression. These results provide evidence that disrupting glutamate clearance in habenular astrocytes increases neuronal excitability and depressive-like phenotypes in behaviors and sleep.