Abstract：
BACKGROUND: Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. This study aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in the paraventricular thalamus to resist anesthetic effects of sevoflurane in mice.
METHODS: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway.
RESULTS: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens.
CONCLUSIONS: Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.
UNASSIGNED:
METHODS: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway.
RESULTS: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens.
CONCLUSIONS: Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.
UNASSIGNED:
摘要：
背景：已发现刺激室旁丘脑可以增强麻醉恢复；但是，全身麻醉药调节室旁丘脑的潜在分子机制尚不清楚。这里,我们的目的是检验以下假设:钠渗漏通道(NALCN)维持室旁丘脑的神经元活性,以抵抗七氟醚对小鼠的麻醉作用.
方法：化学遗传学和光遗传学操作，体内多通道记录，和脑电图记录用于研究室旁丘脑神经元活动在七氟醚麻醉中的作用。应用病毒介导的敲低和/或过表达来确定钠泄漏通道如何影响七氟醚下室旁丘脑谷氨酸能神经元的兴奋性。使用病毒示踪剂和局部场电位来探索下游途径。
结果：七氟醚麻醉抑制了室旁丘脑中的单个神经元尖峰，并在出现时恢复。脑室旁丘脑谷氨酸能神经元的光遗传学激活缩短了七氟醚麻醉的出现期，而化学遗传抑制作用则相反。室旁丘脑钠泄漏通道的敲除延迟了七氟醚麻醉的出现（恢复时间：从24±14到64±19s，P<0.001；恢复正正反射的浓度：从1.13％±0.10％到0.97％±0.13％，P<0.01)。不出所料,室旁丘脑中钠渗漏通道的过度表达产生了相反的作用。在电路级别，室旁丘脑中钠泄漏通道的敲除降低了伏隔核的神经元活性，如局部场电位和伏隔核中单个神经元尖峰减少所示。此外,通过光学刺激伏隔核，可以逆转室旁丘脑钠泄漏通道敲除对七氟醚作用的影响。
结论：钠渗漏通道的活性维持小鼠室旁丘脑谷氨酸能神经元的兴奋性，以抵抗七氟醚的麻醉作用。
方法：化学遗传学和光遗传学操作，体内多通道记录，和脑电图记录用于研究室旁丘脑神经元活动在七氟醚麻醉中的作用。应用病毒介导的敲低和/或过表达来确定钠泄漏通道如何影响七氟醚下室旁丘脑谷氨酸能神经元的兴奋性。使用病毒示踪剂和局部场电位来探索下游途径。
结果：七氟醚麻醉抑制了室旁丘脑中的单个神经元尖峰，并在出现时恢复。脑室旁丘脑谷氨酸能神经元的光遗传学激活缩短了七氟醚麻醉的出现期，而化学遗传抑制作用则相反。室旁丘脑钠泄漏通道的敲除延迟了七氟醚麻醉的出现（恢复时间：从24±14到64±19s，P<0.001；恢复正正反射的浓度：从1.13％±0.10％到0.97％±0.13％，P<0.01)。不出所料,室旁丘脑中钠渗漏通道的过度表达产生了相反的作用。在电路级别，室旁丘脑中钠泄漏通道的敲除降低了伏隔核的神经元活性，如局部场电位和伏隔核中单个神经元尖峰减少所示。此外,通过光学刺激伏隔核，可以逆转室旁丘脑钠泄漏通道敲除对七氟醚作用的影响。
结论：钠渗漏通道的活性维持小鼠室旁丘脑谷氨酸能神经元的兴奋性，以抵抗七氟醚的麻醉作用。
