Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94035, USA.
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA.
Neuron. 2020 May 20;106(4):624-636.e4. doi: 10.1016/j.neuron.2020.02.029. Epub 2020 Mar 18.
The ventral tegmental area (VTA) is a major target of addictive drugs and receives multiple GABAergic projections originating outside the VTA. We describe differences in synaptic plasticity and behavior when optogenetically driving two opiate-sensitive GABAergic inputs to the VTA, the rostromedial tegmental nucleus (RMTg), and the periaqueductal gray (PAG). Activation of GABAergic RMTg terminals in the VTA in vivo is aversive, and low-frequency stimulation induces long-term depression in vitro. Low-frequency stimulation of PAG afferents in vitro unexpectedly causes long-term potentiation. Opioid receptor activation profoundly depresses PAG and RMTg inhibitory synapses but prevents synaptic plasticity only at PAG synapses. Activation of the GABAergic PAG terminals in the VTA promotes immobility, and optogenetically-driven immobility is blocked by morphine. Our data reveal the PAG as a source of highly opioid-sensitive GABAergic afferents and support the idea that different GABAergic pathways to the VTA control distinct behaviors.
腹侧被盖区（VTA）是成瘾药物的主要靶点，它接收来自 VTA 外部的多个 GABA 能投射。我们描述了当光遗传学驱动两个鸦片敏感的 GABA 能输入到 VTA 时，即延髓腹侧正中核（RMTg）和导水管周围灰质（PAG），在突触可塑性和行为上的差异。在体内激活 VTA 中的 GABA 能 RMTg 末梢是令人厌恶的，低频刺激会在体外诱导长期抑郁。体外刺激 PAG 传入纤维的低频刺激会导致长期增强。阿片受体的激活深度抑制 PAG 和 RMTg 的抑制性突触，但仅在 PAG 突触处阻止突触可塑性。激活 VTA 中的 GABA 能 PAG 末梢会促进不动性，而光遗传学驱动的不动性被吗啡阻断。我们的数据揭示了 PAG 作为高度阿片敏感的 GABA 能传入的来源，并支持这样的观点，即 VTA 的不同 GABA 能途径控制不同的行为。
