Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks
Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks
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DOI：
10.1073/pnas.1523717113
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发表时间：
2016-05-10
影响因子：
11.1
通讯作者：
Goda, Yukiko
中科院分区：
文献类型：
--
作者：
Letellier, Mathieu;Park, Yun Kyung;Goda, Yukiko
树突是专门用于通过其许多突触输入接收和处理信息的神经元结构。对于突触整合和可塑性至关重要的输入强度是如何在树突之间进行修改的，目前还不清楚。我们研究了单个海马神经元的异突触相互作用的机制和锥体细胞输入的突触强度的异质性。平衡输入强度的异突触前可塑性需要N-甲基-D-天冬氨酸受体（NMDAR）和星形胶质细胞。重要的是，这种机制与维持高度异质性基础突触前强度的机制是相同的，这需要星形胶质细胞Ca2+信号传导，涉及NMDAR激活、星形胶质细胞膜去极化和L型Ca2+通道。细胞内输注NMDAR或Ca2+通道阻滞剂进入星形胶质细胞，有条件地消融GluN1 NMDAR亚基，或光遗传学超极化星形胶质细胞与古视紫红质促进收敛突触前输入的均质化。我们的研究结果支持存在星形胶质细胞依赖的细胞机制，增强了会聚连接的突触前强度的异质性，这可能有助于提高树突的计算能力。
Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the mechanism of heterosynaptic interactions and the heterogeneity of synaptic strengths of pyramidal cell inputs. Heterosynaptic presynaptic plasticity that counterbalances input strengths requires N-methyl-D-aspartate receptors (NMDARs) and astrocytes. Importantly, this mechanism is shared with the mechanism for maintaining highly heterogeneous basal presynaptic strengths, which requires astrocyte Ca2+ signaling involving NMDAR activation, astrocyte membrane depolarization, and L-type Ca2+ channels. Intracellular infusion of NMDARs or Ca2+-channel blockers into astrocytes, conditionally ablating the GluN1 NMDAR subunit, or optogenetically hyperpolarizing astrocytes with archaerhodopsin promotes homogenization of convergent presynaptic inputs. Our findings support the presence of an astrocyte-dependent cellular mechanism that enhances the heterogeneity of presynaptic strengths of convergent connections, which may help boost the computational power of dendrites.