美国哥伦比亚大学Steven A. Siegelbaum团队取得最新进展。他们研究了海马CA2区社交新颖性的编码及其在22q11.2微缺失小鼠模型中的破坏和拯救。相关论文于2020年10月19日发表于《自然-神经科学》。

为了确定CA2活性是否编码社交互动，他们在社交行为期间从雄性小鼠的CA2锥体神经元（PNs）进行细胞外记录。尽管CA2神经元放电仅显示出较弱的空间选择性，但它可以准确地编码环境变化，并可以区分新小鼠和熟悉的小鼠。在人类22q11.2微缺失的Df（16）A +/-小鼠模型中，精神分裂症的风险增加了30倍，CA2社交编码受损，与这些小鼠中观察到的社交记忆缺陷一致，但是空间编码精度大大提高。

先前发现CA2 PNs在Df（16）A +/-小鼠中超极化，可能是由于TREK-1 K +电流的上调所致。他们发现TREK-1阻滞物拯救了Df（16）A +/-小鼠的社交记忆和CA2社交编码，并支持CA2在社交刺激的正常编码和疾病中社交行为障碍中的关键作用。

据悉，海马CA2区对于社交记忆至关重要。

附：英文原文

Title: Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a 22q11.2 microdeletion mouse model

Author: Macayla L. Donegan, Fabio Stefanini, Torcato Meira, Joshua A. Gordon, Stefano Fusi, Steven A. Siegelbaum

Issue&Volume: 2020-10-19

Abstract: The hippocampal CA2 region is essential for social memory. To determine whether CA2 activity encodes social interactions, we recorded extracellularly from CA2 pyramidal neurons (PNs) in male mice during social behavior. Although CA2 neuronal firing showed only weak spatial selectivity, it accurately encoded contextual changes and distinguished between a novel and a familiar mouse. In the Df(16)A+/ mouse model of the human 22q11.2 microdeletion, which confers a 30-fold increased risk of schizophrenia, CA2 social coding was impaired, consistent with the social memory deficit observed in these mice; in contrast, spatial coding accuracy was greatly enhanced. CA2 PNs were previously found to be hyperpolarized in Df(16)A+/ mice, likely due to upregulation of TREK-1 K+ current. We found that TREK-1 blockade rescued social memory and CA2 social coding in Df(16)A+/ mice, supporting a crucial role for CA2 in the normal encoding of social stimuli and in social behavioral dysfunction in disease.

DOI: 10.1038/s41593-020-00720-5

Source: https://www.nature.com/articles/s41593-020-00720-5