| First Author | Luo Y | Year | 2024 |
| Journal | Transl Psychiatry | Volume | 14 |
| Issue | 1 | Pages | 325 |
| PubMed ID | 39107319 | Mgi Jnum | J:358789 |
| Mgi Id | MGI:7708618 | Doi | 10.1038/s41398-024-03043-2 |
| Citation | Luo Y, et al. (2024) Reduced excitatory activity in the developing mPFC mediates a PV(H)-to-PV(L) transition and impaired social cognition in autism spectrum disorders. Transl Psychiatry 14(1):325 |
| abstractText | 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. |
