Table_5_A Temporal Activity of CA1 Neurons Underlying Short-Term Memory for Social Recognition Altered in PTEN Mouse Models of Autism Spectrum Disorder.DOCX

Memory-guided social recognition identifies someone from previous encounters or experiences, but the mechanisms of social memory remain unclear. Here, we find that a short-term memory from experiencing a stranger mouse lasting under 30 min interval is essential for subsequent social recognition in mice, but that interval prolonged to hours by replacing the stranger mouse with a familiar littermate. Optogenetic silencing of dorsal CA1 neuronal activity during trials or inter-trial intervals disrupted short-term memory-guided social recognition, without affecting the ability of being sociable or long-term memory-guided social recognition. Postnatal knockdown or knockout of autism spectrum disorder (ASD)-associated phosphatase and tensin homolog (PTEN) gene in dorsal hippocampal CA1 similarly impaired neuronal firing rate in vitro and altered firing pattern during social recognition. These PTEN mice showed deficits in social recognition with stranger mouse rather than littermate and exhibited impairment in T-maze spontaneous alternation task for testing short-term spatial memory. Thus, we suggest that a temporal activity of dorsal CA1 neurons may underlie formation of short-term memory to be critical for organizing subsequent social recognition but that is possibly disrupted in ASD.

记忆驱动社交识别（memory-guided social recognition）指通过过往接触或经历识别同类的能力，但目前社交记忆的相关机制仍未明确。本研究发现，小鼠在30分钟内与陌生小鼠接触形成的短时记忆，对后续的社交识别行为至关重要；而当用熟悉的同窝小鼠替换陌生小鼠时，该记忆的维持时长可延长至数小时。在试验阶段或试验间隔期间对海马背侧CA1区神经元活动进行光遗传沉默，会破坏短时记忆驱动的社交识别能力，但不会影响小鼠的社交倾向或长时记忆驱动的社交识别能力。在海马背侧CA1区出生后敲低或敲除自闭症谱系障碍（autism spectrum disorder, ASD）相关的张力蛋白同源物（phosphatase and tensin homolog, PTEN）基因，同样会在体外降低神经元放电速率，并改变社交识别过程中的神经元放电模式。这类PTEN工程小鼠仅在识别陌生小鼠（而非同窝小鼠）时存在社交识别缺陷，并且在用于检测短时空间记忆的T迷宫自发交替任务中表现出功能受损。综上，本研究提示海马背侧CA1神经元的时序性活动可能是短时记忆形成的基础，而该短时记忆对后续社交识别的调控至关重要；这一过程可能在自闭症谱系障碍中受到破坏。