Cues predicting rewards can gain motivational properties and initiate reward-seeking behaviors. Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) are critical in regulating cue-motivated responding. Although, approximately one third of mesoaccumbal projection neurons are GABAergic, it is unclear how this population influences motivational processes and cue processing. This is largely due to our inability to pharmacologically probe circuit level contributions of VTA-GABA, which arises from diverse sources, including multiple GABA afferents, interneurons, and projection neurons. Here we used a combinatorial viral vector approach to restrict activating Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to GABA neurons in the VTA of wild-type rats trained to respond during a distinct audiovisual cue for sucrose. We measured different aspects of motivation for the cue or primary reinforcer, while chemogenetically activating either the VTA-GABA neurons or their projections to the NAc. Activation of VTA-GABA neurons decreased cue-induced responding and accuracy, while increasing latencies to respond to the cue and obtain the reward. Perseverative and spontaneous responses decreased, yet the rats persisted in entering the reward cup when the cue and reward were absent. However, activation of the VTA-GABA terminals in the accumbens had no effect on any of these behaviors. Together, we demonstrate that VTA-GABA neuron activity preferentially attenuates the ability of cues to trigger reward-seeking, while some aspects of the motivation for the reward itself are preserved. Additionally, the dense VTA-GABA projections to the NAc do not influence the motivational salience of the cue.

中文翻译：

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腹侧被盖区 GABA 神经元的化学遗传学激活，而不是 mesoaccumbal GABA 末端，会破坏对奖励预测线索的响应。

预测奖励的线索可以获得激励特性并引发寻求奖励的行为。从腹侧被盖区 (VTA) 到伏隔核 (NAc) 的多巴胺投射对于调节提示动机的反应至关重要。虽然，大约三分之一的 mesoaccumbal 投射神经元是 GABAergic，但尚不清楚这一群体如何影响动机过程和提示处理。这主要是由于我们无法从药理学上探测 VTA-GABA 的电路水平贡献，它来自多种来源，包括多个 GABA 传入、中间神经元和投射神经元。在这里，我们使用组合病毒载体方法将由设计药物 (DREADD) 独家激活的设计受体限制为野生型大鼠 VTA 中的 GABA 神经元，这些神经元被训练在对蔗糖的独特视听提示期间作出反应。我们测量了提示或初级强化物动机的不同方面，同时化学激活 VTA-GABA 神经元或其对 NAc 的投射。VTA-GABA 神经元的激活降低了提示诱导的响应和准确性，同时增加了响应提示和获得奖励的延迟。持久性和自发性反应减少，但当提示和奖励不存在时，大鼠坚持进入奖励杯。然而，伏隔核中 VTA-GABA 末端的激活对这些行为没有任何影响。一起，我们证明 VTA-GABA 神经元活动优先削弱线索触发寻求奖励的能力，而奖励本身的动机的某些方面被保留。此外，对 NAc 的密集 VTA-GABA 投影不会影响提示的动机显着性。