The ventral subiculum (vSUB), the major output structure of the hippocampal formation, regulates motivation, stress integration, and anxiety-like behaviors that rely on heightened arousal. However, the roles and underlying neural circuits of the vSUB in wakefulness are poorly known. Using in vivo fiber photometry and multichannel electrophysiological recordings in mice, we found that the vSUB glutamatergic neurons exhibited high activities during wakefulness. Moreover, activation of vSUB glutamatergic neurons caused an increase in wakefulness and anxiety-like behaviors and induced a rapid transition from sleep to wakefulness. In addition, optogenetic stimulation of vSUB glutamatergic terminals and retrograde-targeted chemogenetic activation of vSUB glutamatergic neurons revealed that vSUB promoted arousal by innervating the lateral hypothalamus (LH), nucleus accumbens (NAc) shell, and prefrontal cortex (PFC). Nevertheless, local microinjection of dopamine D1 or D2/D3 receptor antagonist blocked the wake-promoting effect induced by chemogenetic activation of vSUB pathways. Finally, chemogenetic inhibition of vSUB glutamatergic neurons decreased arousal. Altogether, our findings reveal a prominent contribution of vSUB glutamatergic neurons to the control of wakefulness through several pathways.

腹侧下托（vSUB）是海马结构的主要输出结构，调节依赖于高度唤醒的动机、压力整合和焦虑样行为。然而，人们对 vSUB 在清醒状态中的作用和潜在神经回路知之甚少。利用小鼠体内纤维光度测定和多通道电生理记录，我们发现 vSUB 谷氨酸能神经元在清醒期间表现出高活性。此外，vSUB 谷氨酸能神经元的激活导致觉醒和焦虑样行为的增加，并诱导从睡眠到觉醒的快速转变。此外，vSUB谷氨酸能末端的光遗传学刺激和vSUB谷氨酸能神经元的逆行靶向化学遗传学激活表明，vSUB通过神经支配下丘脑外侧（LH）、伏隔核（NAc）壳和前额皮质（PFC）来促进觉醒。然而，局部显微注射多巴胺 D1 或 D2/D3 受体拮抗剂阻断了 vSUB 途径的化学遗传学激活诱导的促醒作用。最后，vSUB 谷氨酸能神经元的化学遗传学抑制降低了觉醒。总而言之，我们的研究结果揭示了 vSUB 谷氨酸能神经元通过多种途径对觉醒的控制做出了显着贡献。