Research Service (151A3), Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, Los Angeles, CA 91343, USA.
Department of Psychiatry, University of California, Los Angeles, CA 90095, USA.
Int J Mol Sci. 2023 May 5;24(9):8311. doi: 10.3390/ijms24098311.
The ventrolateral preoptic area (VLPO) contains GABAergic sleep-active neurons. However, the extent to which these neurons are involved in expressing spontaneous sleep and homeostatic sleep regulatory demands is not fully understood. We used calcium (Ca) imaging to characterize the activity dynamics of VLPO neurons, especially those expressing the vesicular GABA transporter (VGAT) across spontaneous sleep-waking and in response to homeostatic sleep demands. The VLPOs of wild-type and VGAT-Cre mice were transfected with GCaMP6, and the Ca fluorescence of unidentified (UNID) and VGAT cells was recorded during spontaneous sleep-waking and 3 h of sleep deprivation (SD) followed by 1 h of recovery sleep. Although both VGAT and UNID neurons exhibited heterogeneous Ca fluorescence across sleep-waking, the majority of VLPO neurons displayed increased activity during nonREM/REM (VGAT, 120/303; UNID, 39/106) and REM sleep (VGAT, 32/303; UNID, 19/106). Compared to the baseline waking, VLPO sleep-active neurons ( = 91) exhibited higher activity with increasing SD that remained elevated during the recovery period. These neurons also exhibited increased Ca fluorescence during nonREM sleep, marked by increased slow-wave activity and REM sleep during recovery after SD. These findings support the notion that VLPO sleep-active neurons, including GABAergic neurons, are components of neuronal circuitry that mediate spontaneous sleep and homeostatic responses to sustained wakefulness.
腹外侧视前区 (VLPO) 含有 GABA 能睡眠活性神经元。然而，这些神经元在表达自发性睡眠和稳态睡眠调节需求方面的参与程度尚不完全清楚。我们使用钙（Ca）成像来描述 VLPO 神经元的活动动力学，特别是那些在自发性睡眠-觉醒期间以及在响应稳态睡眠需求时表达囊泡 GABA 转运体（VGAT）的神经元。野生型和 VGAT-Cre 小鼠的 VLPO 用 GCaMP6 转染，并在自发性睡眠-觉醒期间以及 3 小时睡眠剥夺（SD）后 1 小时恢复睡眠期间记录未鉴定（UNID）和 VGAT 细胞的 Ca 荧光。尽管 VGAT 和 UNID 神经元在睡眠-觉醒期间均表现出异质 Ca 荧光，但大多数 VLPO 神经元在非快速眼动/快速眼动（VGAT，120/303；UNID，39/106）和快速眼动睡眠（VGAT，32/303；UNID，19/106）期间表现出增加的活性。与基线清醒相比，VLPO 睡眠活性神经元（=91）在 SD 期间表现出更高的活性，并且在恢复期间仍然升高。这些神经元在非快速眼动睡眠期间也表现出 Ca 荧光增加，这表现为在 SD 后恢复期间慢波活动和 REM 睡眠增加。这些发现支持 VLPO 睡眠活性神经元（包括 GABA 能神经元）是介导自发性睡眠和对持续觉醒的稳态反应的神经元回路的组成部分的观点。
