Department of Neuroscience, Zuckerman and Kavli Institutes, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
Nat Neurosci. 2020 Nov;23(11):1365-1375. doi: 10.1038/s41593-020-00720-5. Epub 2020 Oct 19.
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.
海马体 CA2 区对于社会记忆至关重要。为了确定 CA2 活动是否对社交互动进行编码，我们在雄性小鼠进行社交行为时，从 CA2 锥体神经元（PN）中记录了细胞外电活动。尽管 CA2 神经元的放电仅表现出微弱的空间选择性，但它能够准确地编码上下文变化，并区分新的和熟悉的小鼠。在人类 22q11.2 微缺失的 Df(16)A 小鼠模型中，22q11.2 微缺失会使精神分裂症的风险增加 30 倍，CA2 的社交编码受损，与这些小鼠中观察到的社会记忆缺陷一致；相比之下，空间编码准确性大大提高。先前发现 Df(16)A 小鼠中的 CA2 PN 被超极化，这可能是由于 TREK-1 K 电流的上调。我们发现，TREK-1 阻断可挽救 Df(16)A 小鼠的社会记忆和 CA2 的社交编码，这支持 CA2 在正常编码社交刺激以及在疾病中的社交行为功能障碍中发挥关键作用。
