Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, USA; College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, 19129, USA.
Neuropharmacology. 2022 Feb 15;204:108895. doi: 10.1016/j.neuropharm.2021.108895. Epub 2021 Nov 20.
Social memory is the ability to discriminate familiar conspecific from the unknown ones. Prefrontal neurons are essentially required for social memory, but the mechanism associated with this regulation remains unknown. It is also unclear to what extent the neuronal representations of social memory formation and retrieval events overlap in the prefrontal cortex (PFC) and which event drives social memory strength. Here we asked these questions by using a repeated social training paradigm for social recognition in FosTRAP mice. We found that after 4 days' repeated social training, female mice developed stable social memory. Specifically, repeated social training activated more cells that were labeled with tdTomato during memory retrieval compared with the first day of memory encoding. Besides, combining TRAP with c-Fos immunostaining, we found about 30% of the FosTRAPed cells were reactivated during retrieval. Moreover, the number of retrieval-induced but not first-day encoding-induced tdTomato neurons correlates with the social recognition ratio in the prelimbic but not other subregions. The activated cells during the retrieval session also showed increased NMDA receptor-mediated synaptic transmission compared with that in non-labeled pyramidal neurons. Blocking NMDA receptors by MK-801 impaired social memory but not sociability. Therefore, our results reveal that repetitive training elevates mPFC involvement in social memory retrieval via enhancing NMDA receptor-mediated synaptic transmission, thus rendering stable social memory.
社会记忆是区分熟悉同种个体与陌生个体的能力。前额叶神经元对于社会记忆是必不可少的，但与这种调节相关的机制仍不清楚。前额叶皮层（PFC）中社会记忆形成和检索事件的神经元表征在多大程度上重叠，以及哪个事件驱动社会记忆强度，这些问题也尚未得到解答。在这里，我们通过在 FosTRAP 小鼠中使用重复社交训练范式来研究社交识别，从而回答了这些问题。我们发现，经过 4 天的重复社交训练，雌性小鼠形成了稳定的社交记忆。具体来说，与第一天的记忆编码相比，重复的社交训练在记忆检索时激活了更多标记有 tdTomato 的细胞。此外，通过结合 TRAP 和 c-Fos 免疫染色，我们发现大约 30%的 FosTRAPed 细胞在检索时被重新激活。此外，在检索过程中诱导的而非第一天编码诱导的 tdTomato 神经元的数量与前扣带回但不是其他亚区的社会识别率相关。与未标记的锥体神经元相比，在检索过程中激活的细胞还显示出 NMDA 受体介导的突触传递增加。用 MK-801 阻断 NMDA 受体可损害社交记忆，但不损害社交能力。因此，我们的结果表明，重复训练通过增强 NMDA 受体介导的突触传递来提高 mPFC 参与社会记忆检索，从而产生稳定的社会记忆。
