Synapse-specific expression of calcium-permeable AMPA receptors in neocortical layer 5.
Synapse-specific expression of calcium-permeable AMPA receptors in neocortical layer 5.
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DOI：
10.1113/jp271394
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发表时间：
2016-02-15
期刊：
影响因子：
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通讯作者：
Sjöström PJ
中科院分区：
文献类型：
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作者：
Lalanne T;Oyrer J;Mancino A;Gregor E;Chung A;Huynh L;Burwell S;Maheux J;Farrant M;Sjöström PJ
在海马体中，钙渗透性AMPA受体已被发现存在于抑制其他神经元的神经元类型的有限子集中，尽管它们在新皮质中的定位尚不清楚。在本研究中，我们在两个不同的新皮层抑制性神经元群体中寻找钙渗透性AMPA受体：篮状细胞和Martinotti细胞。我们在前者中发现了它们，但在后者中没有发现。此外，在篮状细胞中，这些受体与特别快的反应有关。计算机模型预测（实验证实），快速钙渗透AMPA受体使篮状细胞能够迅速反应，从而迅速抑制邻近细胞并关闭活动。本研究中获得的结果有助于我们理解与钙渗透性AMPA受体调节紊乱相关的病理学，如中风和癫痫。缺乏编辑的GluA 2亚基的AMPA型谷氨酸受体（AMPAR）是钙渗透性的（CP），并有助于几种海马中间神经元类型的突触可塑性，尽管它们在新皮层中的确切作用尚未得到很好的描述。我们探索了CP-AMPAR在发育中的小鼠视觉皮层（出生后12-21天）的第5层中的锥体细胞（PC）输入到Martinotti细胞（MC）和篮状细胞（BC）的存在。GluA 2免疫标记在MCs中比在BCs中更强。基于精胺依赖性整流和1-萘基乙酰精胺对CP-AMPAR阻断的测量，使用突触连接细胞对的记录、NPEC-AMPA撑开和微型电流记录，在电生理学上证实了PC-BC和PC-MC突触中CP-AMPAR的差异存在。此外，BCs中的CP-AMPAR表达与快速衰减的突触电流相关。计算机建模预测，这减少了尖峰潜伏期和锐化阈值上的反应，在BC，我们验证了实验使用动态钳技术。因此，CP-AMPAR的突触特异性表达可能会严重影响新皮层微回路中的可塑性和信息处理。在海马体中，钙渗透性AMPA受体已被发现存在于抑制其他神经元的神经元类型的有限子集中，尽管它们在新皮质中的定位尚不清楚。在本研究中，我们在两个不同的新皮层抑制性神经元群体中寻找钙渗透性AMPA受体：篮状细胞和Martinotti细胞。我们在前者中发现了它们，但在后者中没有发现。此外，在篮状细胞中，这些受体与特别快的反应有关。计算机模型预测（实验证实），快速钙渗透AMPA受体使篮状细胞能够迅速反应，从而迅速抑制邻近细胞并关闭活动。本研究中获得的结果有助于我们理解与钙渗透性AMPA受体调节紊乱相关的病理学，如中风和癫痫。
In the hippocampus, calcium‐permeable AMPA receptors have been found in a restricted subset of neuronal types that inhibit other neurons, although their localization in the neocortex is less well understood. In the present study, we looked for calcium‐permeable AMPA receptors in two distinct populations of neocortical inhibitory neurons: basket cells and Martinotti cells. We found them in the former but not in the latter. Furthermore, in basket cells, these receptors were associated with particularly fast responses. Computer modelling predicted (and experiments verified) that fast calcium‐permeable AMPA receptors enable basket cells to respond rapidly, such that they promptly inhibit neighbouring cells and shut down activity. The results obtained in the present study help our understanding of pathologies such as stroke and epilepsy that have been associated with disordered regulation of calcium‐permeable AMPA receptors. AMPA‐type glutamate receptors (AMPARs) lacking an edited GluA2 subunit are calcium‐permeable (CP) and contribute to synaptic plasticity in several hippocampal interneuron types, although their precise role in the neocortex is not well described. We explored the presence of CP‐AMPARs at pyramidal cell (PC) inputs to Martinotti cells (MCs) and basket cells (BCs) in layer 5 of the developing mouse visual cortex (postnatal days 12–21). GluA2 immunolabelling was stronger in MCs than in BCs. A differential presence of CP‐AMPARs at PC‐BC and PC‐MC synapses was confirmed electrophysiologically, based on measures of spermine‐dependent rectification and CP‐AMPAR blockade by 1‐naphtyl acetyl spermine using recordings from synaptically connected cell pairs, NPEC‐AMPA uncaging and miniature current recordings. In addition, CP‐AMPAR expression in BCs was correlated with rapidly decaying synaptic currents. Computer modelling predicted that this reduces spike latencies and sharpens suprathreshold responses in BCs, which we verified experimentally using the dynamic clamp technique. Thus, the synapse‐specific expression of CP‐AMPARs may critically influence both plasticity and information processing in neocortical microcircuits. In the hippocampus, calcium‐permeable AMPA receptors have been found in a restricted subset of neuronal types that inhibit other neurons, although their localization in the neocortex is less well understood. In the present study, we looked for calcium‐permeable AMPA receptors in two distinct populations of neocortical inhibitory neurons: basket cells and Martinotti cells. We found them in the former but not in the latter. Furthermore, in basket cells, these receptors were associated with particularly fast responses. Computer modelling predicted (and experiments verified) that fast calcium‐permeable AMPA receptors enable basket cells to respond rapidly, such that they promptly inhibit neighbouring cells and shut down activity. The results obtained in the present study help our understanding of pathologies such as stroke and epilepsy that have been associated with disordered regulation of calcium‐permeable AMPA receptors.