Astrocyte Signaling Gates Long-Term Depression at Corticostriatal Synapses of the Direct Pathway
Astrocyte Signaling Gates Long-Term Depression at Corticostriatal Synapses of the Direct Pathway
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DOI：
10.1523/jneurosci.2369-19.2020
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发表时间：
2020-07-22
影响因子：
5.3
通讯作者：
Araque, Alfonso
中科院分区：
文献类型：
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作者：
Cavaccini, Anna;Durkee, Caitlin;Araque, Alfonso
尽管对纹状体可塑性的突触机制进行了广泛的研究，但星形胶质细胞在这一区域所起的功能作用仍有待充分阐明。最近的研究表明，高频刺激（HFS）的皮层输入诱导长时程抑制（LTD）介导的腺苷A1受体（A1 R）激活的直接途径[皮质-纹状体投射神经元（dSPN）]在背外侧纹状体（DLS）的皮质纹状体突触。由于星形胶质细胞衍生的腺苷已被证明可以调节几个脑区的突触传递，我们研究了这种形式的神经元-星形胶质细胞信号传导是否有助于雄性和雌性小鼠DLS的突触可塑性。我们发现，皮质HFS通过激活代谢型谷氨酸受体5型（mGluR 5）信号传导增加纹状体星形胶质细胞中的钙（Ca 2+）水平，并且这种星形胶质细胞介导的反应是A1 R介导的LTD所必需的。与此一致，星形胶质细胞激活Gq设计者受体（DREADDs）在皮质-dSPN突触处诱导A1 R介导的突触抑制。总之，这些结果表明，星形胶质细胞是纹状体A1 R介导的LTD的组成部分。
Despite extensive research into understanding synaptic mechanisms of striatal plasticity, the functional role played by astro-cytes in this region remains to be fully elucidated. It was recently demonstrated that high-frequency stimulation (HFS) of cortical inputs induced long-term depression (LTD) mediated by adenosine A1 receptor (A1R) activation at corticostriatal synapses of the direct pathway [cortico-striatal projection neuron (dSPN)] in the dorsolateral striatum (DLS). Because astro-cyte-derived adenosine has been shown to regulate synaptic transmission in several brain areas, we investigated whether this form of neuron-astrocyte signaling contributes to synaptic plasticity in the DLS of male and female mice. We found that cort-ical HFS increases calcium (Ca2+) levels in striatal astrocytes through activation of metabotropic glutamate receptor type 5 (mGluR5) signaling and that this astrocyte-mediated response is necessary for A1R-mediated LTD. Consistent with this, astro-cyte activation with Gq designer receptors exclusively activated by designer drugs (DREADDs) induced A1R-mediated synaptic depression at cortico-dSPN synapses. Together, these results indicate that astrocytes are integral elements of striatal A1R-mediated LTD.