Neuroscience
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Oxytocin (OT) is a key factor for maternal behavior. However, neurochemical regulation of OT neurons, the major source of OT, remains incompletely understood. Here we report the effect of intranasally-applied OT (IAO) on OT neuronal activity in the supraoptic nucleus (SON) and on maternal behavior in a rat model of cesarean delivery (CD) at day 4-5 (stage I) and day 8-9 (stage II) following delivery. ⋯ In brain slices, CD but not CD plus IAO significantly depolarized membrane potential and increased spike duration in OT neurons. In vasopressin neurons, CD, but not CD plus IAO, significantly depolarized membrane potential and increased the firing rate. Thus, decreased OT neuronal activity and increased vasopressin neuronal activity impair maternal behavior in CD dams, which can be prevented by IAO .
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Sensory disturbance in the orofacial region owing to trigeminal nerve injury is caused by dental treatment or accident. Commercially available therapeutics are ineffective for the treatment of sensory disturbance. Additionally, the therapeutic effects of rapamycin, an allosteric inhibitor of mammalian target of rapamycin (mTOR), which negatively regulates autophagy, on the sensory disturbance are not fully investigated. ⋯ Rapamycin administration facilitated axon regeneration after IANX and increased the number of brain-derived neurotrophic factor positive neurons in the trigeminal ganglion. Thus, recovery from sensory disturbance in the lower lip caused by IANX was markedly facilitated by rapamycin. These findings suggest that rapamycin administration is a promising treatment for the sensory disturbance caused by IANX.
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Endocannabinoids are bioactive substances which participate in central motor control. The globus pallidus (GP) is a major nucleus in the basal ganglia circuit, which plays an important function in movement regulation. Both cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R) are expressed in the GP suggesting GP as a main action area of endocannabinoids. ⋯ Finally, both haloperidol-induced postural behavioral test and elevated body swing test (EBST) showed that unilateral microinjection of WIN 55,212-2 mainly induced contralateral-biased swing and deflection behaviors. Meanwhile, AM 251 produced opposite effect. The present in vivo study revealed that cannabinoids produced complicated electrophysiological and behavioral effects in the GP, which further demonstrated that the GP is a major functional region of endocannabinoid.
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Alterations in thalamic GABAergic signaling are implicated in mediating the rise in 12-30 Hz electroencephalogram (EEG) activity that signals anesthetic-induced loss-of-consciousness with GABAA receptor-targeting general anesthetics. A number of modeling studies have identified that anesthetic-induced alterations in thalamocortico-corticothalamic signaling in the same network that generates sleep spindles would be sufficient to elicit this key EEG signature of anesthetic hypnosis with general anesthetic agents. Accordingly, we hypothesize that targeted stimulation of this thalamic GABAergic circuitry into a sleep-spindle mode of activity would promote the general anesthetic effects of etomidate. ⋯ Optical spindle-rhythm stimulation prolonged the increase in 12-30 Hz activity in ChR2-VGAT mice only (p = 0.023). Spindle-rhythm stimulation also increased the incidence and duration of sleep spindle-like oscillations in ChR2-VGAT mice only (all p ≤ 0.001). Despite the maintained anesthetic-like changes in EEG activity, optical spindle-rhythm stimulation was not associated with changes in the time to and duration of the loss-of-righting reflex, a behavioral endpoint of etomidate-induced general anesthesia in rodents.
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Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a crucial regulator of neuronal development, neuronal survival, axonal regeneration, and synaptic plasticity. In this study we examined the potential role of PTEN in cognitive function in a mouse model of perioperative neurocognitive disorder (PND). Adult male C57BL/6J mice received intracerebroventricular injections of small interfering RNA (siRNA) against PTEN or control siRNA 3 days prior to exploratory laparotomy (n = 8 per group). ⋯ Surgically treated mice had increased expression of PTEN, AMPK, Bax, IL-1β, and TNF-α, as well as increasing number of activated microglia and apoptosis neurons in the hippocampus. PTEN knockdown significantly attenuated the behavioral deficits in Barnes maze and fear conditioning tests, as well as over-expression of PTEN, AMPK, Bax, IL-1β, and TNF-α induced by surgery. PTEN knockdown could attenuate cognitive deficits induced by trauma, likely through inhibiting the activation of microglia.