Distinct extended amygdala circuits for divergent motivational states.
Distinct extended amygdala circuits for divergent motivational states.
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作者：
在成瘾和抑郁等疾病中，焦虑和奖励处理功能障碍的共病表明，共同的神经回路导致了这些不同的神经精神症状。延伸的杏仁核，包括终纹床核（BNST），调节恐惧和焦虑，但也投射到腹侧被盖区（VTA），这是一个与奖励和厌恶有关的区域，从而为整合不同的情绪状态提供了候选神经基底。然而，不同的BNST投射神经元和它们在腹侧被盖区的突触后靶点之间的精确功能连接，以及该回路在控制动机状态中的作用还没有被描述。在这里，我们记录和操纵活动的遗传和神经化学鉴定腹侧被盖投射BNST神经元在自由行为的小鼠。总的来说，厌恶刺激暴露产生的VTA投射BNST神经元的异质性放电模式。与此相反，在体内光学鉴定的GABA能投射神经元表现出净增强的活动厌恶刺激，而确定的GABA能投射神经元的放电率被抑制。视紫红质-2（ChR 2）辅助的电路映射显示，BNST多巴胺能和GABA能投射优先支配突触后非多巴胺能腹侧被盖区神经元，从而提供了一个机制框架，在体内电路扰动。在体内光刺激BNST神经元投射导致厌恶和焦虑的行为表型。相反，激活BNST GABA能投射产生奖励和抗焦虑表型，这也是通过直接抑制腹侧被盖区GABA能神经元重演。这些数据表明，功能上反对BNST VTA电路调节奖励和厌恶的动机状态，并可能作为一个关键的电路节点双向正常化适应不良行为。
The comorbidity of anxiety and dysfunctional reward processing in illnesses such as addiction and depression suggests that common neural circuitry contributes to these disparate neuropsychiatric symptoms. The extended amygdala, including the bed nucleus of the stria terminalis (BNST), modulates fear and anxiety, but also projects to the ventral tegmental area (VTA) , a region implicated in reward and aversion, thus providing a candidate neural substrate for integrating diverse emotional states. However, the precise functional connectivity between distinct BNST projection neurons and their postsynaptic targets in the VTA, as well as the role of this circuit in controlling motivational states have not been described. Here, we recorded and manipulated the activity of genetically and neurochemically identified VTA-projecting BNST neurons in freely behaving mice. Collectively, aversive stimuli exposure produced heterogeneous firing patterns in VTA-projecting BNST neurons. In contrast, in vivo optically-identified glutamatergic projection neurons displayed a net enhancement of activity to aversive stimuli, whereas the firing rate of identified GABAergic projection neurons was suppressed. Channelrhodopsin-2 (ChR2) assisted circuit mapping revealed that both BNST glutamatergic and GABAergic projections preferentially innervate postsynaptic non-dopaminergic VTA neurons, thus providing a mechanistic framework for in vivo circuit perturbations. In vivo photostimulation of BNST glutamatergic projections resulted in aversive and anxiogenic behavioral phenotypes. In contrast, activation of BNST GABAergic projections produced rewarding and anxiolytic phenotypes, which were also recapitulated by direct inhibition of VTA GABAergic neurons. These data demonstrate that functionally opposing BNST to VTA circuits regulate rewarding and aversive motivational states and may serve as a critical circuit node for bidirectionally normalizing maladaptive behaviors.
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DOI：
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