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

doi:10.1038/nn.4257

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

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 language	English (US)
Pages (from-to)	557-559
Number of pages	3
Journal	Nature neuroscience
Volume	19
Issue number	4
DOIs	https://doi.org/10.1038/nn.4257
State	Published - Mar 29 2016

ASJC Scopus subject areas

General Neuroscience

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title = "Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders",

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.",

author = "Wen Zhang and Lifeng Zhang and Bo Liang and David Schroeder and Zhang, {Zhong Wei} and Cox, {Gregory A.} and Yun Li and Lin, {Da Ting}",

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AU - Zhang, Wen

AU - Zhang, Lifeng

AU - Liang, Bo

AU - Schroeder, David

AU - Zhang, Zhong Wei

AU - Cox, Gregory A.

AU - Li, Yun

AU - Lin, Da Ting

PY - 2016/3/29

Y1 - 2016/3/29

N2 - 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.

AB - 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.

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Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders

Abstract

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