The long-range GABAergic input from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is relatively understudied, and therefore its role in reward processing has remained unknown. In the present study, we show, in both male and female mice, that long-range GABAergic projections from the VTA to the ventral NAc shell, but not to the dorsal NAc shell or NAc core, are engaged in reward and reinforcement behavior. We show that this GABAergic projection exclusively synapses on to cholinergic interneurons (CINs) in the ventral NAc shell, thereby serving a specialized function in modulating reinforced reward behavior through the inhibition of ventral NAc shell CINs. These findings highlight the diversity in the structural and functional topography of VTA GABAergic projections, and their neuromodulatory interactions across the dorsoventral gradient of the NAc shell. They also further our understanding of neuronal circuits that are directly implicated in neuropsychiatric conditions such as depression and addiction.

从腹侧被盖区 (VTA) 到伏隔核 (NAc) 的远程 GABA 能输入相对较少，因此其在奖励处理中的作用仍然未知。在本研究中，我们表明，在雄性和雌性小鼠中，从 VTA 到腹侧 NAc 壳而不是到背侧 NAc 壳或 NAc 核心的远程 GABA 能投射参与奖励和强化行为。我们表明，这种 GABAergic 投射专门突触到腹侧 NAc 壳中的胆碱能中间神经元 (CIN)，从而通过抑制腹侧 NAc 壳 CIN 在调节强化奖赏行为方面发挥特殊功能。这些发现突出了 VTA GABAergic 投射的结构和功能地形的多样性，以及它们在 NAc 壳背腹梯度上的神经调节相互作用。它们还进一步加深了我们对与抑郁和成瘾等神经精神疾病直接相关的神经元回路的理解。