Abstract
Neuregulin-1 (NRG1), a regulator of neural development, has been shown to regulate neurotransmission at excitatory synapses. Although ErbB4, a key NRG1 receptor, is expressed in glutamic acid decarboxylase (GAD)-positive neurons, little is known about its role in GABAergic transmission. We show that ErbB4 is localized at GABAergic terminals of the prefrontal cortex. Our data indicate a role of NRG1, both endogenous and exogenous, in regulation of GABAergic transmission. This effect was blocked by inhibition or mutation of ErbB4, suggesting the involvement of ErbB4. Together, these results indicate that NRG1 regulates GABAergic transmission via presynaptic ErbB4 receptors, identifying a novel function of NRG1. Because both NRG1 and ErbB4 have emerged as susceptibility genes of schizophrenia, these observations may suggest a mechanism for abnormal GABAergic neurotransmission in this disorder.
Original language | English |
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Pages (from-to) | 599-610 |
Number of pages | 12 |
Journal | Neuron |
Volume | 54 |
Issue number | 4 |
DOIs | |
Publication status | Published - May 24 2007 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank Ren-ping Zhou for providing the pC4 vector, M. Slikowski for NRG1, and Xiangdong Zhu for TAT protein constructs. This work was supported in part by grants from NIH (L.M. and W.C.X.), MDA (L.M.), and NSFC (#30330240 and U0632007, T.M.G.). T.M.G. and L.M. are Chang Jiang Scholars. R.S.W. was supported in part by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, KRF-2004-214-H00004).
ASJC Scopus Subject Areas
- General Neuroscience