Neuregulin3 Regulation of Glutamatergic Transmission

Hdl Handle:
http://hdl.handle.net/10675.2/592517
Title:
Neuregulin3 Regulation of Glutamatergic Transmission
Authors:
Figueiredo, Dwight
Abstract:
Synapses are fundamental communication units in the brain, essential for meaningful response to stimuli received from the environment. Abnormal synaptic communication leads to mental disorders. My studies focus on Neuregulin3, a member of the Neuregulin family. Single Nucleotide Polymorphisms (SNPs) within the NRG3 gene are associated with schizophrenia in different populations. Analysis of postmortem human brain samples of schizophrenia patients revealed abnormal levels of NRG3. However, unlike its well-studied family member NRG1, NRG3’s role in synaptic transmission is not understood. I studied how depletion of Nrg3 protein in the brain could affect synaptic transmission. I measured the amplitude and the frequency of spontaneous as well as miniature Excitatory Post Synaptic Currents (sEPSC and mEPSC, respectively) at hippocampal CA1 neurons of GFAP::Cre;Nrg3f/f mice. I observed changes in synaptic strength at excitatory synapses but not inhibitory synapses. I took advantage of our conditional knockout mice to generate a cell specific knockout of Nrg3. Results demonstrate that Nrg3 regulates synaptic transmission in a neuron-type-specific manner. Further, electrophysiological analysis revealed that synaptic deficits may account for changes in synaptic strength of GFAP::Cre;Nrg3f/f mice. Golgi as well as Electron Microscopy was used to analyze spine number, synaptic vesicle density, and Post Synaptic Density (PSD) structures. I observed no changes in PSD density, length or area, however, I detected structural alterations in the presynaptic terminals of GFAP::Cre;Nrg3f/f mice. Biochemical studies did detect changes in synaptic protein expression levels in GFAP::Cre;Nrg3f/f mice. Anxiety, cognitive as well as social related behavioral paradigms are currently being tested in GFAP::Cre;Nrg3f/f mice.
Affiliation:
Department of Neuroscience and Regenerative Medicine
Issue Date:
Dec-2015
URI:
http://hdl.handle.net/10675.2/592517
Type:
Dissertation
Appears in Collections:
Department of Neuroscience & Regenerative Medicine Theses and Dissertations; Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorFigueiredo, Dwighten
dc.date.accessioned2015-12-22T14:42:09Zen
dc.date.available2015-12-22T14:42:09Zen
dc.date.issued2015-12en
dc.identifier.urihttp://hdl.handle.net/10675.2/592517en
dc.description.abstractSynapses are fundamental communication units in the brain, essential for meaningful response to stimuli received from the environment. Abnormal synaptic communication leads to mental disorders. My studies focus on Neuregulin3, a member of the Neuregulin family. Single Nucleotide Polymorphisms (SNPs) within the NRG3 gene are associated with schizophrenia in different populations. Analysis of postmortem human brain samples of schizophrenia patients revealed abnormal levels of NRG3. However, unlike its well-studied family member NRG1, NRG3’s role in synaptic transmission is not understood. I studied how depletion of Nrg3 protein in the brain could affect synaptic transmission. I measured the amplitude and the frequency of spontaneous as well as miniature Excitatory Post Synaptic Currents (sEPSC and mEPSC, respectively) at hippocampal CA1 neurons of GFAP::Cre;Nrg3f/f mice. I observed changes in synaptic strength at excitatory synapses but not inhibitory synapses. I took advantage of our conditional knockout mice to generate a cell specific knockout of Nrg3. Results demonstrate that Nrg3 regulates synaptic transmission in a neuron-type-specific manner. Further, electrophysiological analysis revealed that synaptic deficits may account for changes in synaptic strength of GFAP::Cre;Nrg3f/f mice. Golgi as well as Electron Microscopy was used to analyze spine number, synaptic vesicle density, and Post Synaptic Density (PSD) structures. I observed no changes in PSD density, length or area, however, I detected structural alterations in the presynaptic terminals of GFAP::Cre;Nrg3f/f mice. Biochemical studies did detect changes in synaptic protein expression levels in GFAP::Cre;Nrg3f/f mice. Anxiety, cognitive as well as social related behavioral paradigms are currently being tested in GFAP::Cre;Nrg3f/f mice.en
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.en
dc.subjectSynapsesen
dc.subjectSynaptic Transmissionen
dc.subjectMiceen
dc.subjectNeuregulinsen
dc.titleNeuregulin3 Regulation of Glutamatergic Transmissionen
dc.typeDissertationen
dc.contributor.departmentDepartment of Neuroscience and Regenerative Medicineen
dc.description.advisorMei, Linen
dc.description.committeeDarrell, Brann; Wen-cheng, Xiong; Krishnan, Dhandhapani; Wei-hua, Wuen
dc.description.degreeDoctor of Philosophy with a Major in Neuroscienceen
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