PDF(Pubmed)
Abstract：
Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.
摘要：
了解自闭症谱系障碍（ASD）中社会认知受损的神经发病机制具有挑战性。在ASD中一直观察到皮质小白蛋白阳性（PV）中间神经元的改变，但是他们的作用和潜在机制仍然知之甚少。在我们的研究中,我们在ASD小鼠模型的内侧前额叶皮质(mPFC)中观察到由于PV+神经元活性降低而导致的PV表达谱向下移动。令人惊讶的是,在出生后发育过程中化学抑制PV神经元活性未能诱导ASD样行为。相比之下,降低发育中的mPFC中的兴奋性活动不仅抑制了单个PV神经元的活动状态和PV表达，但也复制了类似ASD的社会赤字。此外，增强激励，但不是PV+中间神经元介导的抑制，ASD小鼠模型中的救助社会缺陷。总的来说，我们的发现表明，正在发育的mPFC中的兴奋性活动减少可能是一种共享的局部电路机制，可触发PV中间神经元的改变并介导ASD中受损的社会功能。
