Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France.
Aix Marseille University, CNRS, Institut de Neurosciences de la Timone (INT), 13005 Marseille, France.
Cell Rep. 2022 Jul 5;40(1):111034. doi: 10.1016/j.celrep.2022.111034.
Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinson's disease. How this signal regulates the striatal network remains an open question. Here, we examine the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium spiny neurons expressing dopamine D1 receptor (D1 MSNs). Brief interruption of CIN activity has no effect in control conditions, whereas it increases glutamatergic responses in D1 MSNs after dopamine denervation. This potentiation depends upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by optogenetics/chemogenetics in vivo partially rescues long-term potentiation in MSNs and motor learning deficits in parkinsonian mice. Our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs.
纹状体胆碱能中间神经元 (CINs) 在经过短暂的活动暂停后，对显著或与奖励预测相关的刺激产生反应，这表明它们参与了学习和动作选择。在帕金森病的动物模型中，这种暂停消失了。这种信号如何调节纹状体网络仍然是一个悬而未决的问题。在这里，我们研究了 CIN 放电抑制对表达多巴胺 D1 受体 (D1 MSNs) 的皮质和中等棘突神经元之间谷氨酸能传递的影响。在对照条件下，CIN 活动的短暂中断没有影响，而在多巴胺去神经后，它会增加 D1 MSNs 中的谷氨酸能反应。这种增强依赖于 M4 毒蕈碱受体和蛋白激酶 A。在体内通过光遗传学/化学遗传学降低 CIN 的放电，部分挽救了帕金森病小鼠中 MSNs 的长时程增强和运动学习缺陷。我们的发现表明，CINs 对皮质纹状体传递和纹状体依赖性运动技能学习的控制取决于多巴胺能输入的完整性。
