Deep brain stimulation of the subthalamic nucleus (STN) is an effective therapy for motor deficits in Parkinson’s disease (PD), but commonly causes weight gain in late-phase PD patients probably by increasing feeding motivation. It is unclear how STN neurons represent and modulate feeding behavior in different internal states. In the present study, we found that feeding caused a robust activation of STN neurons in mice (GCaMP6 signal increased by 48.4% ± 7.2%, n = 9, P = 0.0003), and the extent varied with the size, valence, and palatability of food, but not with the repetition of feeding. Interestingly, energy deprivation increased the spontaneous firing rate (8.5 ± 1.5 Hz, n = 17, versus 4.7 ± 0.7 Hz, n = 18, P = 0.03) and the depolarization-induced spikes in STN neurons, as well as enhanced the STN responses to feeding. Optogenetic experiments revealed that stimulation and inhibition of STN neurons respectively reduced (by 11% ± 6%, n = 6, P = 0.02) and enhanced (by 36% ± 15%, n = 7, P = 0.03) food intake only in the dark phase. In conclusion, our results support the hypothesis that STN neurons are activated by feeding behavior, depending on energy homeostatic status and the palatability of food, and modulation of these neurons is sufficient to regulate food intake.

丘脑底核 (STN) 的深部脑刺激是治疗帕金森病 (PD) 运动缺陷的有效疗法，但通常可能通过增加进食动机导致晚期 PD 患者体重增加。目前尚不清楚 STN 神经元如何表示和调节不同内部状态下的进食行为。在本研究中，我们发现喂食导致小鼠 STN 神经元的强烈激活（GCaMP6 信号增加了 48.4% ± 7.2%，n = 9，P = 0.0003），并且程度随大小、价态和适口性而变化食物，但不是重复喂食。有趣的是，能量剥夺增加了自发放电率（8.5 ± 1.5 Hz，n = 17，而4.7 ± 0.7 Hz，n= 18, P = 0.03) 和 STN 神经元中去极化诱导的尖峰，以及增强 STN 对进食的反应。光遗传学实验表明，刺激和抑制 STN 神经元分别减少（11% ± 6%，n = 6，P = 0.02）和增加（36% ± 15%，n = 7，P = 0.03）食物摄入量仅在黑暗阶段。总之，我们的结果支持 STN 神经元被摄食行为激活的假设，这取决于能量稳态状态和食物的适口性，并且这些神经元的调节足以调节食物摄入。