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.

记忆引导下的社会识别能够识别前次遭遇或经验中的人物，然而社会记忆的机制尚不明确。本研究发现，在老鼠中，经历陌生人小鼠后30分钟内的短期记忆对于后续的社会识别至关重要，而将陌生人小鼠替换为熟悉的同胞小鼠后，这一间隔可延长至数小时。在试验或试验间隔期间通过光遗传学沉默背侧CA1神经元的活性，破坏了由短期记忆引导的社会识别，但并未影响社交能力或长期记忆引导的社会识别。在体外，通过出生后敲低或敲除自闭症谱系障碍（ASD）相关磷酸酶和张力蛋白同源物（PTEN）基因，同样损害了背侧海马CA1区域的神经元放电频率，并改变了社会识别过程中的放电模式。这些PTEN小鼠在与陌生人小鼠而非同胞小鼠的社会识别中表现出缺陷，并在测试短期空间记忆的T迷宫自发交替任务中表现出障碍。因此，我们提出，背侧CA1神经元的时序活动可能是形成短期记忆的基础，这种记忆对于组织后续的社会识别至关重要，但在自闭症谱系障碍中可能受到破坏。