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
Externally publishedYes

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Interneurons
Somatostatin
Neurodegenerative Diseases
Pyramidal Cells
Pathology
Frontotemporal Dementia With Motor Neuron Disease
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zhang, W., Zhang, L., Liang, B., Schroeder, D., Zhang, Z. W., Cox, G. A., ... 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

Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders. / Zhang, Wen; Zhang, Lifeng; Liang, Bo; Schroeder, David; Zhang, Zhong Wei; Cox, Gregory A.; Li, Yun; Lin, Da Ting.

In: Nature Neuroscience, Vol. 19, No. 4, 29.03.2016, p. 557-559.

Research output: Contribution to journalArticle

Zhang, W, Zhang, L, Liang, B, Schroeder, D, Zhang, ZW, Cox, GA, Li, Y & Lin, DT 2016, 'Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders', Nature Neuroscience, vol. 19, no. 4, pp. 557-559. https://doi.org/10.1038/nn.4257
Zhang, Wen ; Zhang, Lifeng ; Liang, Bo ; Schroeder, David ; Zhang, Zhong Wei ; Cox, Gregory A. ; Li, Yun ; Lin, Da Ting. / Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders. In: Nature Neuroscience. 2016 ; Vol. 19, No. 4. pp. 557-559.
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