Table_3_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从先前遭遇或经验中识别某人，但社会记忆的机制尚不明确。本研究发现，在老鼠中，经历陌生小鼠且间隔时间不超过30分钟的短期记忆对于随后的社会识别至关重要；而通过将陌生小鼠替换为熟悉的小鼠，该间隔时间延长至数小时。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，破坏了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。在背侧海马CA1中，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，同样损害了体外神经元放电频率，并改变了社会识别过程中的放电模式。这些PTEN小鼠在与陌生小鼠而非同胞小鼠的社会识别中表现出缺陷，并在T迷宫自发交替任务中表现出短期空间记忆的损害。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以组织后续社会识别的基础，但这一过程可能在自闭症中受到破坏。