Neuromodulation of Cortical and Subcortical Circuits Laboratory, Neuroscience and Brain Technologies Department, Istituto Italiano di Tecnologia, Genova, Italy.
Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy; Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy.
Neuron. 2018 May 16;98(4):801-816.e7. doi: 10.1016/j.neuron.2018.04.008. Epub 2018 Apr 26.
Monoaminergic modulation of cortical and thalamic inputs to the dorsal striatum (DS) is crucial for reward-based learning and action control. While dopamine has been extensively investigated in this context, the synaptic effects of serotonin (5-HT) have been largely unexplored. Here, we investigated how serotonergic signaling affects associative plasticity at glutamatergic synapses on the striatal projection neurons of the direct pathway (dSPNs). Combining chemogenetic and optogenetic approaches reveals that impeding serotonergic signaling preferentially gates spike-timing-dependent long-term depression (t-LTD) at thalamostriatal synapses. This t-LTD requires dampened activity of the 5-HT4 receptor subtype, which we demonstrate controls dendritic Ca signals by regulating BK channel activity, and which preferentially localizes at the dendritic shaft. The synaptic effects of 5-HT signaling at thalamostriatal inputs provide insights into how changes in serotonergic levels associated with behavioral states or pathology affect striatal-dependent processes.
单胺能调制皮层和丘脑传入到背侧纹状体（DS）对于基于奖励的学习和动作控制至关重要。虽然多巴胺在这方面已经被广泛研究，但 5-羟色胺（5-HT）的突触效应在很大程度上仍未被探索。在这里，我们研究了 5-羟色胺能信号如何影响直接通路（dSPNs）纹状体投射神经元上谷氨酸能突触的联想性可塑性。结合化学遗传学和光遗传学方法表明，抑制 5-羟色胺能信号优先门控丘脑纹状体突触的时程依赖长时程压抑（t-LTD）。这种 t-LTD 需要抑制 5-HT4 受体亚型的活性，我们证明该受体通过调节 BK 通道活性来控制树突 Ca 信号，并且该受体优先定位于树突干。5-羟色胺能信号在丘脑纹状体传入中的突触效应为我们提供了一些线索，了解与行为状态或病理学相关的 5-羟色胺水平变化如何影响纹状体依赖的过程。
