1. Reduced excitatory activity in the developing mPFC mediates a PVH-to-PVL transition and impaired social cognition in autism spectrum disorders
- Author
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Yujian Luo, Liangliang Wang, Yirong Cao, Ying Shen, Yan Gu, and Lang Wang
- Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
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.
- Published
- 2024
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