GABAergic malfunction in the anterior cingulate cortex underlying maternal immune activation-induced social deficits
GABAergic malfunction in the anterior cingulate cortex underlying maternal immune activation-induced social deficits
复制标题
DOI：
10.1016/j.jneuroim.2018.06.006
复制
发表时间：
2018-08-15
影响因子：
3.3
通讯作者：
Ikegaya, Yuji
中科院分区：
文献类型：
--
作者：
Okamoto, Kazuki;Hitora-Imamura, Natsuko;Ikegaya, Yuji
社交缺陷是精神疾病的主要症状之一，包括自闭症谱系障碍（ASD）和精神分裂症。然而，根本机制仍然不明确。在这里，我们重点关注接受聚 (I:C) 诱导的母体免疫激活的小鼠的前扣带皮层 (ACC)，这是一个与社会行为相关的大脑区域。经过聚（I:C）处理的母鼠所产下的后代在幼年阶段的三室任务中表现出社交缺陷。使用全细胞膜片钳记录，我们发现与盐水处理的小鼠相比，在聚（I:C）处理的小鼠制备的急性 ACC 切片中，2/3 层锥体细胞过度活跃。过度兴奋与抑制性突触活性的降低有关。将 GABA A 受体增强剂氯硝西泮局部注射到经聚 (I:C) 治疗的小鼠的 ACC 中，可恢复小鼠的社交行为。这些结果表明 ACC 神经元的平衡兴奋性对于社交能力至关重要。
Social deficits are one of the major symptoms of psychiatric disorders, including autism spectrum disorders (ASDs) and schizophrenia. However, the underlying mechanism remains ill-defined. Here, we focused on the anterior cingulate cortex (ACC), a brain region that is related to social behaviors, of mice that received poly(I:C)induced maternal immune activation. Offspring born from poly(I:C)-treated dams exhibited social deficits in a three-chamber task at juvenile stages. Using whole-cell patch clamp recordings, we found that layer 2/3 pyramidal cells were hyperactive in acute ACC slices prepared from poly(I:C)-treated mice compared to those from saline-treated mice. The hyperexcitation was associated with a reduction in inhibitory synapse activity. Local injection of the GABA A receptor enhancer clonazepam into the ACC of poly(I:C)-treated mice restored the social behaviors of the mice. These results suggest that the balanced excitability of ACC neurons is essential for social ability.