Parasubthalamic calretinin neurons modulate wakefulness associated with exploration in male mice.

The parasubthalamic nucleus (PSTN) is considered to be involved in motivation, feeding and hunting, all of which are highly depending on wakefulness. However, the roles and underlying neural circuits of the PSTN in wakefulness remain unclear. Neurons expressing calretinin (CR) account for the majority of PSTN neurons. In this study in male mice, fiber photometry recordings showed that the activity of PSTNCR neurons increased at the transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep, as well as exploratory behavior. Chemogenetic and optogenetic experiments demonstrated that PSTNCR neurons were necessary for initiating and/or maintaining arousal associated with exploration. Photoactivation of projections of PSTNCR neurons revealed that they regulated exploration-related wakefulness by innervating the ventral tegmental area. Collectively, our findings indicate that PSTNCR circuitry is essential for the induction and maintenance of the awake state associated with exploration.

Paraventricular thalamus controls consciousness transitions during propofol anaesthesia in mice.

BACKGROUND: The neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly understood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of consciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of consciousness during propofol anaesthesia. METHODS: Polysomnographic recordings and righting reflex test were used to determine the transitions of loss and recovery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under conditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods. RESULTS: Population activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of consciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P=0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P=0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P=0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P=0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical activation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s. CONCLUSIONS: The paraventricular thalamus contributes to the control of consciousness transitions in propofol anaesthesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects.

Lesion of intergeniculate leaflet GABAergic neurons attenuates sleep in mice exposed to light.

Light has immediate effects on sleep in rodents, but the neural pathways underlying the effect remain to be elucidated. The intergeniculate leaflet (IGL) containing GABAergic neurons receives direct retinal inputs. We hypothesized that IGL GABAergic neurons may mediate light-induced sleep. EEG/electromyogram recording, immunohistochemistry, electrophysiology, optogenetics, fiber photometry, behavioral tests, and cell-specific destruction were employed to investigate the role of IGL GABAergic neurons in the regulation of acute light-induced sleep. Here, EEG/electromyogram recordings revealed that acute light exposure during the nocturnal active phase in mice induced a significant increase in non-rapid eye movement and rapid eye movement sleep compared with controls. Immunohistochemistry showed that acute light exposure for 2 hours in the active phase induced an increase in c-Fos expression in the IGL, whereas lights-off in the rest phase inhibited it. Patch clamp coupled with optogenetics demonstrated that retinal ganglion cells had monosynaptic functional connections to IGL GABAergic neurons. Calcium activity by fiber photometry in freely behaving mice showed that light exposure increased the activity of IGL GABAergic neurons. Furthermore, lesion of IGL GABAergic neurons by caspase-3 virus significantly attenuated the sleep-promoting effect of light exposure during active phases. Collectively, these results clearly indicated that the IGL is one of key nuclei mediating light-induced sleep in mice.

Phase-transition and aggregation characteristics of a thermoresponsive dextran derivative in aqueous solutions.

Grafting of poly(N-vinylcaprolactam) side chains onto a hydrophilic dextran backbone was found to provide the dextran with new, thermoresponsive properties in aqueous solutions. Depending on its solution concentration, the resulting dextran derivative could exhibit a temperature-induced phase-transition and critical transition temperature (T(c)). Different anions and cations of added salts, including five potassium salts and five alkali-metal chlorides, were observed to influence the T(c) value of its aqueous solution. Except for potassium iodide, all added salts were found to lower the T(c) value. The addition of the surfactant, cationic cetyltrimethylammonium bromide or anionic sodium dodecyl sulfate, resulted in an increase of the T(c) value. With the help of the Coomassie Brilliant Blue dye as a polarity probe, the formation of hydrophobic aggregates above the T(c) was revealed for this new dextran derivative in aqueous solution.