Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons

Guo He Tan, Yuan Yuan Liu, Xiao Ling Hu, Dongmin Yin, Lin Mei, Zhi Qi Xiong

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Epilepsy is a common and refractory neurological disorder, but the neuronal regulatory mechanisms of epileptogenesis remain largely unclear. Activity-dependent transcription of genes for neurotrophins such as brain-derived neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however, little is known about factors that may act as intrinsic, homeostatic or counterbalancing mechanisms. Using rodent models, here we show that limbic seizure activity upregulated NRG1-ErbB4 signaling and that epileptogenesis was inhibited by infusing NRG1 intracerebrally but exacerbated by neutralizing endogenous NRG1 with soluble ErbB4 extracellular domain, by inhibiting ErbB4 activation or by deleting the Erbb4 gene. Furthermore, specific depletion of ErbB4 in parvalbumin-expressing interneurons abolished NRG1-mediated inhibition of epileptogenesis and promoted kindling progression, resulting in increased spontaneous seizures and exuberant mossy fiber sprouting. In contrast, depleting ErbB4 in CaMKIIÎ ±-positive pyramidal neurons had no effect. Thus, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.

Original languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalNature Neuroscience
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2012

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Neuregulin-1
Parvalbumins
Interneurons
Seizures
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Pyramidal Cells
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Nervous System Diseases
Genes
Rodentia
Epilepsy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons. / Tan, Guo He; Liu, Yuan Yuan; Hu, Xiao Ling; Yin, Dongmin; Mei, Lin; Xiong, Zhi Qi.

In: Nature Neuroscience, Vol. 15, No. 2, 01.02.2012, p. 258-266.

Research output: Contribution to journalArticle

Tan, Guo He ; Liu, Yuan Yuan ; Hu, Xiao Ling ; Yin, Dongmin ; Mei, Lin ; Xiong, Zhi Qi. / Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons. In: Nature Neuroscience. 2012 ; Vol. 15, No. 2. pp. 258-266.
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