Table_4_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.

记忆引导的社会识别能够识别先前遭遇或经历中的人物，然而社会记忆的机制仍不明确。本研究发现，在老鼠中，经历陌生小鼠后，在30分钟以下的短期记忆对于随后的社会识别至关重要；而当用熟悉的小鼠替换陌生小鼠时，这一间隔延长至数小时。在试验或试验间隔期间通过光遗传学沉默背侧CA1神经元活动，会干扰由短期记忆引导的社会识别，但不会影响社交能力或长期记忆引导的社会识别。在背侧海马CA1区域，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，同样会在体外损害神经元放电频率，并在社会识别过程中改变放电模式。这些PTEN小鼠在与陌生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神经元的时空活动可能构成了短期记忆的形成，这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发生了破坏。