Neuregulin1 promotes excitatory synapse development specifically in GABAergic interneurons

Hdl Handle:
http://hdl.handle.net/10675.2/320148
Title:
Neuregulin1 promotes excitatory synapse development specifically in GABAergic interneurons
Authors:
Tin, Kin Lai
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 in GABAergic interneurons, indicating that NRG1 stimulates the formation of new synapses and strengthens existing synapses. In contrast, NRG1 treatment had no consistent 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 amplitude of mEPSCs, providing in vivo evidence that ErbB4 is important in postsynaptic differentiation in interneurons. Taken 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.
Issue Date:
Mar-2010
URI:
http://hdl.handle.net/10675.2/320148
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/205429841?accountid=12365
Type:
Dissertation
Language:
en
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorTin, Kin Laien
dc.date.accessioned2014-06-09T20:05:14Z-
dc.date.available2014-06-09T20:05:14Z-
dc.date.issued2010-03-
dc.identifier.urihttp://hdl.handle.net/10675.2/320148-
dc.description.abstractNeuregulin 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 in GABAergic interneurons, indicating that NRG1 stimulates the formation of new synapses and strengthens existing synapses. In contrast, NRG1 treatment had no consistent 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 amplitude of mEPSCs, providing in vivo evidence that ErbB4 is important in postsynaptic differentiation in interneurons. Taken 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.en
dc.language.isoenen
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/205429841?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.-
dc.subjectNeuregulin1en
dc.subjectSynapseen
dc.subjectPostsynaptic Differentiationen
dc.subjectPSD-95en
dc.subjectInterneuronen
dc.subjectSchizophreniaen
dc.titleNeuregulin1 promotes excitatory synapse development specifically in GABAergic interneuronsen
dc.typeDissertationen
dc.description.advisorMei, Linen
dc.description.committeeNot Listed-
dc.description.degreeDoctor of Philosophy (Ph.D.)-
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