Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice.
Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice.
复制标题
DOI：
10.1038/s41467-023-37248-8
复制
发表时间：
2023-03-29
影响因子：
16.6
通讯作者：
Gould, Elizabeth
中科院分区：
文献类型：
--
作者：
Cope, Elise C.;Wang, Samantha H.;Waters, Renee C.;Gore, Isha R.;Vasquez, Betsy;Laham, Blake J.;Gould, Elizabeth
编码突触支架蛋白的SHANK3基因的突变或缺失与自闭症谱系障碍和费伦-麦克德米德综合征有关，后者与社交记忆障碍有关。Shank3B基因敲除小鼠也表现出社会记忆缺陷。海马的CA2区整合了大量的输入，并向腹侧CA1 （vCA1）发送一个主要的输出。尽管在Shank3B基因敲除小鼠中发现CA2的兴奋性传入事件几乎没有差异，但我们发现CA2神经元的激活以及CA2- vca1途径将社会识别功能恢复到野生型水平。vCA1神经元振荡与社会记忆有关，但我们在野生型和Shank3B基因敲除小鼠之间观察到这些指标没有差异。然而，在Shank3B基因敲除小鼠中，CA2的激活增强了vCA1 theta的能力，同时行为也得到改善。这些发现表明，刺激具有神经发育障碍的小鼠模型的成年电路可以调用潜在的社会记忆功能。SHANK3基因与自闭症谱系障碍和费伦·麦克德米德综合征有关，这两种疾病都与社会记忆缺陷有关。在这里，作者展示了Shank3B基因敲除的成年小鼠海马ca2 -腹侧CA1回路的激活可以恢复社会记忆。
Mutation or deletion of the SHANK3 gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments. Shank3B knockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1). Despite finding few differences in excitatory afferents to the CA2 in Shank3B knockout mice, we found that activation of CA2 neurons as well as the CA2-vCA1 pathway restored social recognition function to wildtype levels. vCA1 neuronal oscillations have been linked to social memory, but we observed no differences in these measures between wildtype and Shank3B knockout mice. However, activation of the CA2 enhanced vCA1 theta power in Shank3B knockout mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can invoke latent social memory function. The SHANK3 gene is linked to autism spectrum disorder and Phelan McDermid syndrome, which have been associated with social memory deficits. Here, authors show activation of the hippocampal CA2-ventral CA1 circuit in adult Shank3B knockout mice restores social memory.
登录
查看更多内容
影响因子：
5.3
作者：
Cope, Elise C.;LaMarca, Elizabeth A.;Gould, Elizabeth
通讯作者：
Gould, Elizabeth
影响因子：
16.2
作者：
Amilhon, Benedicte;Huh, Carey Y. L.;Williams, Sylvain
通讯作者：
Williams, Sylvain
影响因子：
3.5
作者：
Buzsáki, G
通讯作者：
Buzsáki, G
影响因子：
3.7
作者：
Al-Onaizi, Mohammed A.;Parfitt, Gustavo M.;Prado, Vania F.
通讯作者：
Prado, Vania F.
影响因子：
11.3
作者：
Kurtz MM;Bronfeld M;Rose J
通讯作者：
Rose J