Sequential inhibitory plasticities in hippocampal area CA2 and social memory formation
Sequential inhibitory plasticities in hippocampal area CA2 and social memory formation
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海马区 CA2 的顺序抑制可塑性与社会记忆形成
DOI：
10.1016/j.neuron.2022.06.013
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发表时间：
2022
期刊：
影响因子：
16.2
通讯作者：
Vivien Chevaleyre
中科院分区：
文献类型：
--
作者：
Maïthé Loisy;G. Bouisset;S. Lopez;M. Muller;Alena Spitsyn;J. Duval;R. Piskorowski;L. Verret;Vivien Chevaleyre
CA 2区是包括社会识别记忆在内的多种海马功能的关键区域。该区域具有独特的属性和连通性。值得注意的是，海马内兴奋性输入CA 2缺乏典型的长期可塑性，但抑制性传递表达了长期抑郁症介导的δ阿片受体（DOR-iLTDs）。有证据表明，DOR-iLTDs不足以成为社会编码的基础。在这里，我们报告了一种新的抑制可塑性介导的大麻素1型受体激活（CB 1 R-iLTD）。令人惊讶的是，CB 1 R-iLTD需要先前诱导DOR-iLTD，表明DOR可塑性的容许作用。在CA 2中阻断CB 1 R完全阻止了社会记忆的形成。此外，DOR和CB 1 R介导的可塑性的顺序性发生在连续的社会互动过程中。最后，CB 1 R-iLTD在具有受损社会认知的精神分裂症小鼠模型中被改变，但通过也挽救社会记忆的操作被挽救。总之，我们的数据揭示了两种抑制可塑性之间的独特相互作用和社会记忆形成的新机制。
Area CA2 is a critical region for diverse hippocampal functions including social recognition memory. This region has unique properties and connectivity. Notably, intra-hippocampal excitatory inputs to CA2 lack canonical long-term plasticity, but inhibitory transmission expresses a long-term depression mediated by Delta-opioid receptors (DOR-iLTDs). Evidence indicates that DOR-iLTDs are insufficient to underlie social coding. Here, we report a novel inhibitory plasticity mediated by cannabinoid type 1 receptor activation (CB1R-iLTD). Surprisingly, CB1R-iLTD requires previous induction of DOR-iLTDs, indicating a permissive role for DOR plasticity. Blockade of CB1Rs in CA2 completely prevents social memory formation. Furthermore, the sequentiality of DOR- and CB1R-mediated plasticity occursin vivoduring successive social interactions. Finally, CB1R-iLTD is altered in a mouse model of schizophrenia with impaired social cognition but is rescued by a manipulation that also rescues social memory. Altogether, our data reveal a unique interplay between two inhibitory plasticities and a novel mechanism for social memory formation.