Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory

Yisheng Lu, Xiang Dong Sun, Feng Qing Hou, Lin Lin Bi, Dong Min Yin, Fang Liu, Yong Jun Chen, Jonathan C. Bean, Hui Feng Jiao, Xihui Liu, Bao Ming Li, Wen Cheng Xiong, Tian Ming Gao, Lin Mei

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Inhibitory neurotransmission in amygdala is important for fear learning and memory. However, mechanisms that control the inhibitory activity in amygdala are not well understood. We provide evidence that neuregulin 1 (NRG1) and its receptor ErbB4 tyrosine kinase are critical for maintaining GABAergic activity in amygdala. Neutralizing endogenous NRG1, inhibition, or genetic ablation of ErbB4, which was expressed in a majority of palvalbumin (PV)+ neurons in amygdala, reduced GABAergic transmission and inhibited tone-cued fear conditioning. Specific ablation of ErbB4 in PV+ neurons reduced eIPSC/eEPSC ratios and impaired fear conditioning. Notably, expression of ErbB4 in amygdala was sufficient to diminish synaptic dysfunction and fear conditioning deficits in PV-ErbB4-/- mice. These observations indicated that NRG1 signaling maintains high GABAergic activity in amygdala and, thus, regulates fear memory. Considering that both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study sheds light on potential pathophysiological mechanisms of this disorder.

Original languageEnglish (US)
Pages (from-to)835-846
Number of pages12
JournalNeuron
Volume84
Issue number4
DOIs
StatePublished - Nov 19 2014

Fingerprint

Neuregulin-1
Amygdala
Fear
Maintenance
Neurons
Receptor Protein-Tyrosine Kinases
Synaptic Transmission
Schizophrenia
Learning
Genes
Conditioning (Psychology)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lu, Y., Sun, X. D., Hou, F. Q., Bi, L. L., Yin, D. M., Liu, F., ... Mei, L. (2014). Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory. Neuron, 84(4), 835-846. https://doi.org/10.1016/j.neuron.2014.09.029

Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory. / Lu, Yisheng; Sun, Xiang Dong; Hou, Feng Qing; Bi, Lin Lin; Yin, Dong Min; Liu, Fang; Chen, Yong Jun; Bean, Jonathan C.; Jiao, Hui Feng; Liu, Xihui; Li, Bao Ming; Xiong, Wen Cheng; Gao, Tian Ming; Mei, Lin.

In: Neuron, Vol. 84, No. 4, 19.11.2014, p. 835-846.

Research output: Contribution to journalArticle

Lu, Y, Sun, XD, Hou, FQ, Bi, LL, Yin, DM, Liu, F, Chen, YJ, Bean, JC, Jiao, HF, Liu, X, Li, BM, Xiong, WC, Gao, TM & Mei, L 2014, 'Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory', Neuron, vol. 84, no. 4, pp. 835-846. https://doi.org/10.1016/j.neuron.2014.09.029
Lu, Yisheng ; Sun, Xiang Dong ; Hou, Feng Qing ; Bi, Lin Lin ; Yin, Dong Min ; Liu, Fang ; Chen, Yong Jun ; Bean, Jonathan C. ; Jiao, Hui Feng ; Liu, Xihui ; Li, Bao Ming ; Xiong, Wen Cheng ; Gao, Tian Ming ; Mei, Lin. / Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory. In: Neuron. 2014 ; Vol. 84, No. 4. pp. 835-846.
@article{cc8706120a2848a89544ea221072f4b6,
title = "Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory",
abstract = "Inhibitory neurotransmission in amygdala is important for fear learning and memory. However, mechanisms that control the inhibitory activity in amygdala are not well understood. We provide evidence that neuregulin 1 (NRG1) and its receptor ErbB4 tyrosine kinase are critical for maintaining GABAergic activity in amygdala. Neutralizing endogenous NRG1, inhibition, or genetic ablation of ErbB4, which was expressed in a majority of palvalbumin (PV)+ neurons in amygdala, reduced GABAergic transmission and inhibited tone-cued fear conditioning. Specific ablation of ErbB4 in PV+ neurons reduced eIPSC/eEPSC ratios and impaired fear conditioning. Notably, expression of ErbB4 in amygdala was sufficient to diminish synaptic dysfunction and fear conditioning deficits in PV-ErbB4-/- mice. These observations indicated that NRG1 signaling maintains high GABAergic activity in amygdala and, thus, regulates fear memory. Considering that both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study sheds light on potential pathophysiological mechanisms of this disorder.",
author = "Yisheng Lu and Sun, {Xiang Dong} and Hou, {Feng Qing} and Bi, {Lin Lin} and Yin, {Dong Min} and Fang Liu and Chen, {Yong Jun} and Bean, {Jonathan C.} and Jiao, {Hui Feng} and Xihui Liu and Li, {Bao Ming} and Xiong, {Wen Cheng} and Gao, {Tian Ming} and Lin Mei",
year = "2014",
month = "11",
day = "19",
doi = "10.1016/j.neuron.2014.09.029",
language = "English (US)",
volume = "84",
pages = "835--846",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory

AU - Lu, Yisheng

AU - Sun, Xiang Dong

AU - Hou, Feng Qing

AU - Bi, Lin Lin

AU - Yin, Dong Min

AU - Liu, Fang

AU - Chen, Yong Jun

AU - Bean, Jonathan C.

AU - Jiao, Hui Feng

AU - Liu, Xihui

AU - Li, Bao Ming

AU - Xiong, Wen Cheng

AU - Gao, Tian Ming

AU - Mei, Lin

PY - 2014/11/19

Y1 - 2014/11/19

N2 - Inhibitory neurotransmission in amygdala is important for fear learning and memory. However, mechanisms that control the inhibitory activity in amygdala are not well understood. We provide evidence that neuregulin 1 (NRG1) and its receptor ErbB4 tyrosine kinase are critical for maintaining GABAergic activity in amygdala. Neutralizing endogenous NRG1, inhibition, or genetic ablation of ErbB4, which was expressed in a majority of palvalbumin (PV)+ neurons in amygdala, reduced GABAergic transmission and inhibited tone-cued fear conditioning. Specific ablation of ErbB4 in PV+ neurons reduced eIPSC/eEPSC ratios and impaired fear conditioning. Notably, expression of ErbB4 in amygdala was sufficient to diminish synaptic dysfunction and fear conditioning deficits in PV-ErbB4-/- mice. These observations indicated that NRG1 signaling maintains high GABAergic activity in amygdala and, thus, regulates fear memory. Considering that both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study sheds light on potential pathophysiological mechanisms of this disorder.

AB - Inhibitory neurotransmission in amygdala is important for fear learning and memory. However, mechanisms that control the inhibitory activity in amygdala are not well understood. We provide evidence that neuregulin 1 (NRG1) and its receptor ErbB4 tyrosine kinase are critical for maintaining GABAergic activity in amygdala. Neutralizing endogenous NRG1, inhibition, or genetic ablation of ErbB4, which was expressed in a majority of palvalbumin (PV)+ neurons in amygdala, reduced GABAergic transmission and inhibited tone-cued fear conditioning. Specific ablation of ErbB4 in PV+ neurons reduced eIPSC/eEPSC ratios and impaired fear conditioning. Notably, expression of ErbB4 in amygdala was sufficient to diminish synaptic dysfunction and fear conditioning deficits in PV-ErbB4-/- mice. These observations indicated that NRG1 signaling maintains high GABAergic activity in amygdala and, thus, regulates fear memory. Considering that both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study sheds light on potential pathophysiological mechanisms of this disorder.

UR - http://www.scopus.com/inward/record.url?scp=84918809931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918809931&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2014.09.029

DO - 10.1016/j.neuron.2014.09.029

M3 - Article

C2 - 25451196

AN - SCOPUS:84918809931

VL - 84

SP - 835

EP - 846

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 4

ER -