Abstract
Neuregulin 1 (NRG1) is a trophic factor thought to play a role in neural development. Recent studies suggest that it may regulate neurotransmission, mechanisms of which remain elusive. Here we show that NRG1, via stimulating GABA release from interneurons, inhibits pyramidal neurons in the prefrontal cortex (PFC). Ablation of the NRG1 receptor ErbB4 in parvalbumin (PV)-positive interneurons prevented NRG1 from stimulating GABA release and from inhibiting pyramidal neurons. PV-ErbB4-/- mice exhibited schizophrenia-relevant phenotypes similar to those observed in NRG1 or ErbB4 null mutant mice, including hyperactivity, impaired working memory, and deficit in prepulse inhibition (PPI) that was ameliorated by diazepam, a GABA enhancer. These results indicate that NRG1 regulates the activity of pyramidal neurons by promoting GABA release from PV-positive interneurons, identifying a critical function of NRG1 in balancing brain activity. Because both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study provides insight into potential pathogenic mechanisms of schizophrenia and suggests that PV-ErbB4-/- mice may serve as a model in the study of this and relevant brain disorders.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1211-1216 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 19 2010 |
Fingerprint
Keywords
- Epilepsy
- GABA
- Neurotransmission
- Schizophrenia
ASJC Scopus subject areas
- General
Cite this
Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons. / Wen, Lei; Lu, Yi Sheng; Zhu, Xin Hong; Li, Xiao Ming; Woo, Ran Sook; Chen, Yong Jun; Yin, Dong Min; Lai, Cary; Terry, Alvin V.; Vazdarjanova, Almira; Xiong, Wen Cheng; Mei, Lin.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 3, 19.01.2010, p. 1211-1216.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons
AU - Wen, Lei
AU - Lu, Yi Sheng
AU - Zhu, Xin Hong
AU - Li, Xiao Ming
AU - Woo, Ran Sook
AU - Chen, Yong Jun
AU - Yin, Dong Min
AU - Lai, Cary
AU - Terry, Alvin V.
AU - Vazdarjanova, Almira
AU - Xiong, Wen Cheng
AU - Mei, Lin
PY - 2010/1/19
Y1 - 2010/1/19
N2 - Neuregulin 1 (NRG1) is a trophic factor thought to play a role in neural development. Recent studies suggest that it may regulate neurotransmission, mechanisms of which remain elusive. Here we show that NRG1, via stimulating GABA release from interneurons, inhibits pyramidal neurons in the prefrontal cortex (PFC). Ablation of the NRG1 receptor ErbB4 in parvalbumin (PV)-positive interneurons prevented NRG1 from stimulating GABA release and from inhibiting pyramidal neurons. PV-ErbB4-/- mice exhibited schizophrenia-relevant phenotypes similar to those observed in NRG1 or ErbB4 null mutant mice, including hyperactivity, impaired working memory, and deficit in prepulse inhibition (PPI) that was ameliorated by diazepam, a GABA enhancer. These results indicate that NRG1 regulates the activity of pyramidal neurons by promoting GABA release from PV-positive interneurons, identifying a critical function of NRG1 in balancing brain activity. Because both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study provides insight into potential pathogenic mechanisms of schizophrenia and suggests that PV-ErbB4-/- mice may serve as a model in the study of this and relevant brain disorders.
AB - Neuregulin 1 (NRG1) is a trophic factor thought to play a role in neural development. Recent studies suggest that it may regulate neurotransmission, mechanisms of which remain elusive. Here we show that NRG1, via stimulating GABA release from interneurons, inhibits pyramidal neurons in the prefrontal cortex (PFC). Ablation of the NRG1 receptor ErbB4 in parvalbumin (PV)-positive interneurons prevented NRG1 from stimulating GABA release and from inhibiting pyramidal neurons. PV-ErbB4-/- mice exhibited schizophrenia-relevant phenotypes similar to those observed in NRG1 or ErbB4 null mutant mice, including hyperactivity, impaired working memory, and deficit in prepulse inhibition (PPI) that was ameliorated by diazepam, a GABA enhancer. These results indicate that NRG1 regulates the activity of pyramidal neurons by promoting GABA release from PV-positive interneurons, identifying a critical function of NRG1 in balancing brain activity. Because both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study provides insight into potential pathogenic mechanisms of schizophrenia and suggests that PV-ErbB4-/- mice may serve as a model in the study of this and relevant brain disorders.
KW - Epilepsy
KW - GABA
KW - Neurotransmission
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=75749110218&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75749110218&partnerID=8YFLogxK
U2 - 10.1073/pnas.0910302107
DO - 10.1073/pnas.0910302107
M3 - Article
C2 - 20080551
AN - SCOPUS:75749110218
VL - 107
SP - 1211
EP - 1216
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 3
ER -