Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders

Wen Zhang, Lifeng Zhang, Bo Liang, David Schroeder, Zhong Wei Zhang, Gregory A. Cox, Yun Li, Da Ting Lin

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Using TDP-43 A315T mice, an ALS and FTD model with marked cortical pathology, we found that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PNs) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PNs and alleviated neurodegeneration, suggesting a new therapeutic target for ALS and FTD.

Original languageEnglish (US)
Pages (from-to)557-559
Number of pages3
JournalNature neuroscience
Volume19
Issue number4
DOIs
StatePublished - Mar 29 2016

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zhang, W., Zhang, L., Liang, B., Schroeder, D., Zhang, Z. W., Cox, G. A., Li, Y., & Lin, D. T. (2016). Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders. Nature neuroscience, 19(4), 557-559. https://doi.org/10.1038/nn.4257