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

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48 Scopus citations

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

ASJC Scopus subject areas

  • Neuroscience(all)

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    Lu, Y., Sun, X. D., Hou, F. Q., Bi, L. L., Yin, D. M., Liu, F., Chen, Y. J., Bean, J. C., Jiao, H. F., Liu, X., Li, B. M., Xiong, W. C., Gao, T. M., & 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