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dc.contributor.authorLin, Thiri W.
dc.date.accessioned2017-11-02T19:21:13Z
dc.date.available2017-11-02T19:21:13Z
dc.date.issued11/2/2017en
dc.identifier.urihttp://hdl.handle.net/10675.2/621651
dc.descriptionThe file you are attempting to access is currently restricted to Augusta University. Please log in with your NetID if off campus.Record is embargoed until 11/02/2019en
dc.description.abstractGABA activity has been implicated in neural development; however, in vivo genetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied postnatal synapse development in ErbB4-Vgat-/- mice where Vgat was deleted in ErbB4+ interneurons. We show that the number of inhibitory axo-somatic synapses onto pyramidal neurons is layer-specific; however, inhibitory synapses on axon initial segments (AISs) were similar from layer to layer. On the other hand, PV+ErbB4+ interneurons and PV-only interneurons receive higher number of inhibitory synapses from PV+ErbB4+ interneurons, compared with ErbB4-only interneurons. Erbb4-Vgat-/- mice exhibited fewer inhibitory synapses from PV+ErbB4+ interneurons onto excitatory neurons (either axo-somatic or axo-axonic), compared with control mice. The Vgat mutation seemed to have little effect on inhibitory synapses onto PV+ and/or ErbB4+ interneurons. These morphological alterations were associated with concomitant changes in neurotransmission. Finally, perineuronal nets were increased in the cortex of ErbB4-Vgat-/- mice. These results demonstrate that GABA activity from ErbB4+ interneurons specifically regulates the development of inhibitory synapses onto excitatory neurons and provides in vivo evidence for a critical role of GABA activity in circuit assembly.
dc.titleREGULATION OF SYNAPSE DEVELOPMENT BY GABA ACTIVITY OF ERBB4-POSITIVE INTERNEURONSen
dc.typeDissertationen
dc.contributor.departmentDepartment of Neuroscience and Regenerative Medicineen
dc.language.rfc3066en
dc.date.updated2017-11-02T19:21:13Z
dc.description.advisorMei, Linen
dc.description.degreeDoctor of Philosophy (Ph.D.)en
dc.description.committeeBrann, Darrell; Dhandapani, Kris; Wang, Phillip; Xiong, Wen-Chengen
html.description.abstractGABA activity has been implicated in neural development; however, in vivo genetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied postnatal synapse development in ErbB4-Vgat-/- mice where Vgat was deleted in ErbB4+ interneurons. We show that the number of inhibitory axo-somatic synapses onto pyramidal neurons is layer-specific; however, inhibitory synapses on axon initial segments (AISs) were similar from layer to layer. On the other hand, PV+ErbB4+ interneurons and PV-only interneurons receive higher number of inhibitory synapses from PV+ErbB4+ interneurons, compared with ErbB4-only interneurons. Erbb4-Vgat-/- mice exhibited fewer inhibitory synapses from PV+ErbB4+ interneurons onto excitatory neurons (either axo-somatic or axo-axonic), compared with control mice. The Vgat mutation seemed to have little effect on inhibitory synapses onto PV+ and/or ErbB4+ interneurons. These morphological alterations were associated with concomitant changes in neurotransmission. Finally, perineuronal nets were increased in the cortex of ErbB4-Vgat-/- mice. These results demonstrate that GABA activity from ErbB4+ interneurons specifically regulates the development of inhibitory synapses onto excitatory neurons and provides in vivo evidence for a critical role of GABA activity in circuit assembly.


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