Loisy Maïthé, Bouisset Guillaume, Lopez Sébastien, Muller Maud, Spitsyn Alena, Duval Jeanne, Piskorowski Rebecca Ann, Verret Laure, Chevaleyre Vivien
Université Paris Cité, INSERM U1266, Institute of Psychiatry and Neuroscience of Paris, 75014 Paris, France.
Research Center on Animal Cognition, Center for Integrative Biology, Toulouse University, CNRS, UPS, 31062 Toulouse, France.
Neuron. 2022 Sep 7;110(17):2854-2866.e4. doi: 10.1016/j.neuron.2022.06.013. Epub 2022 Jul 19.
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 occurs in vivo during 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.
CA2区是海马体多种功能（包括社会识别记忆）的关键区域。该区域具有独特的特性和连接性。值得注意的是，海马体内向CA2区的兴奋性输入缺乏典型的长期可塑性，但抑制性传递表现出由δ-阿片受体介导的长期抑制（DOR-iLTDs）。有证据表明，DOR-iLTDs不足以作为社会编码的基础。在此，我们报告了一种由1型大麻素受体激活介导的新型抑制性可塑性（CB1R-iLTD）。令人惊讶的是，CB1R-iLTD需要先前诱导DOR-iLTDs，这表明DOR可塑性具有许可作用。阻断CA2区的CB1Rs会完全阻止社会记忆的形成。此外，DOR和CB1R介导的可塑性的顺序性在连续的社会互动过程中在体内发生。最后，CB1R-iLTD在社会认知受损的精神分裂症小鼠模型中发生改变，但通过一种也能挽救社会记忆的操作得以恢复。总之，我们的数据揭示了两种抑制性可塑性之间独特的相互作用以及社会记忆形成的新机制。
