Sköld Johan, Lazzarino Gisela Paola, Nett Myra, Wiskerke Joost, Engblom David
Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
iScience. 2025 Apr 16;28(5):112456. doi: 10.1016/j.isci.2025.112456. eCollection 2025 May 16.
The dopaminergic system is crucial for affect regulation. Melanocortin 4 receptors (MC4R) in the ventral striatum have been shown to be necessary for establishing aversive states. Here, we functionally characterize MC4R-expressing striatal neurons in mice. MC4Rs were enriched in atypical dopamine receptor 1 (D1) neurons in the lateral stripe of the striatum (LSS), an understudied area in the ventrolateral striatum. Fiber photometry recordings showed that MC4R neuron activity and local dopamine release in the LSS increased in response to both rewarding and aversive stimuli. Moreover, MC4R neuronal activity and glutamate release in the LSS correlated with body movement. Optogenetic activation of MC4R-LSS neurons was rewarding in a real-time place preference test and a self-stimulation paradigm, increased locomotor activity, and induced striatal dopamine release. Collectively, our findings suggest that MC4R-LSS neurons are activated by stimuli of both rewarding and aversive character and that they induce positive affect, dopamine release and locomotion.
多巴胺能系统对情感调节至关重要。腹侧纹状体中的黑皮质素4受体（MC4R）已被证明对建立厌恶状态是必要的。在这里，我们对小鼠中表达MC4R的纹状体神经元进行功能特性分析。MC4R在纹状体外侧条带（LSS）的非典型多巴胺受体1（D1）神经元中富集，LSS是腹外侧纹状体中一个研究较少的区域。纤维光度记录显示，LSS中的MC4R神经元活动和局部多巴胺释放对奖赏性和厌恶性刺激均有增加。此外，LSS中的MC4R神经元活动和谷氨酸释放与身体运动相关。在实时位置偏好测试和自我刺激范式中，MC4R-LSS神经元的光遗传学激活具有奖赏作用，增加了运动活动，并诱导了纹状体多巴胺释放。总的来说，我们的研究结果表明，MC4R-LSS神经元被具有奖赏性和厌恶性特征的刺激激活，并且它们诱导积极情感、多巴胺释放和运动。
