Neuregulin 1 Promotes Excitatory Synapse Development and Function in GABAergic Interneurons
Open Access
- 5 January 2011
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (1), 15-25
- https://doi.org/10.1523/jneurosci.2538-10.2011
Abstract
Neuregulin 1 (NRG1) and its receptor ErbB4 are both susceptibility genes of schizophrenia. However, little is known about the underlying mechanisms of their malfunction. Although ErbB4 is enriched in GABAergic interneurons, the role of NRG1 in excitatory synapse formation in these neurons remains poorly understood. We showed that NRG1 increased both the number and size of PSD-95 puncta and the frequency and amplitude of miniature EPSCs (mEPSCs) in GABAergic interneurons, indicating that NRG1 stimulates the formation of new synapses and strengthens existing synapses. In contrast, NRG1 treatment had no effect on either the number or size of excitatory synapses in glutamatergic neurons, suggesting its synaptogenic effect is specific to GABAergic interneurons. Ecto-ErbB4 treatment diminished both the number and size of excitatory synapses, suggesting that endogenous NRG1 may be critical for basal synapse formation. NRG1 could stimulate the stability of PSD-95 in the manner that requires tyrosine kinase activity of ErbB4. Finally, deletion of ErbB4 in parvalbumin-positive interneurons led to reduced frequency and amplitude of mEPSCs, providingin vivoevidence that ErbB4 is important in excitatory synaptogenesis in interneurons. Together, our findings suggested a novel synaptogenic role of NRG1 in excitatory synapse development, possibly via stabilizing PSD-95, and this effect is specific to GABAergic interneurons. In light of the association of the genes of both NRG1 and ErbB4 with schizophrenia and dysfunction of GABAergic system in this disorder, these results provide insight into its potential pathological mechanism.Keywords
This publication has 53 references indexed in Scilit:
- Dopamine D1 receptor-mediated NMDA receptor insertion depends on Fyn but not Src kinase pathway in prefrontal cortical neuronsMolecular Brain, 2010
- Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneuronsProceedings of the National Academy of Sciences of the United States of America, 2009
- Selective Expression of ErbB4 in Interneurons, But Not Pyramidal Cells, of the Rodent HippocampusJournal of Neuroscience, 2009
- Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout miceHippocampus, 2009
- Neuregulin 1 in neural development, synaptic plasticity and schizophreniaNature Reviews Neuroscience, 2008
- Dynamic Aspects of CNS Synapse FormationAnnual Review of Neuroscience, 2007
- The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and PlasticityNeuron, 2007
- Stimulated ErbB4 internalization is necessary for neuregulin signaling in neuronsBiochemical and Biophysical Research Communications, 2007
- Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5′ SNPs associated with the diseaseProceedings of the National Academy of Sciences of the United States of America, 2006
- Tangential Neuronal Migration Controls Axon Guidance: A Role for Neuregulin-1 in Thalamocortical Axon NavigationCell, 2006