{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"The Role of Type III-Nrg1 signaling in excitatory transmission in the nucleus accumbens","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/76523"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Nrg1-ErbB4 signaling is important for the maintenance of synaptic plasticity, and the fine-tuning of GABAergic, dopaminergic, cholinergic and glutamatergic neurotransmission. The Type III-isoforms of Nrg1 are predominantly targeted to dendrites and axons, and are expressed by the principal neurons of the hippocampus, cortex and amygdala. These neurons all send glutamatergic inputs into the nucleus accumbens, which expresses the Nrg1 receptor ErbB4. Integration of the information encoded by these Nrg1-expressing inputs, together with midbrain dopamine inputs is crucial for normal functioning of the accumbens. Based on the expression pattern of Type III-Nrg1 and its receptor, ErbB4, I propose that presynaptic Type III- Nrg1/postsynaptic ErbB4 signaling may play an important role in modulating excitatory transmission within accumbens circuits. Type III-Nrg1 heterozygous mice display (i) deficient functional connectivity between the ventral hippocampus and the nucleus accumbens, and (ii) alterations in behaviors in which the ventral hippocampus-accumbens circuit plays a role. Based on these findings, I hypothesize that Type III-Nrg1/ErbB4 signaling is required for the appropriate establishment and maturation of glutamatergic transmission within accumbens circuits. Here, I shed light on the distinct accumbens neuro-circuitry that participates in Nrg1/ErbB4 signaling, by defining the specific accumbens neuronal population that expresses ErbB4. We investigated the pattern of expression of ErbB4 in the accumbens during critical stages of development: at perinatal ages (P0-P3), during the ages when accumbens neurons undergo maturation (adolescence, P20-P23) and in adulthood (>P60). I also investigated the role of Nrg1 in the regulation of accumbens glutamatergic transmission by delineating the glutamate receptor profile of the accumbens. My major findings are that: a. ErbB4 expression is widespread in perinatal accumbens but becomes limited to few cells in adults, b. The subcellular distribution of ErbB4 changes during maturation from somatic at birth, to dendritic and post synaptic compartments, c. Type III-Nrg1 genotype, but not ErbB4 genotype, modulates the flop vs flip exon usage specificity of GluA1 transcripts during maturation and d. The alternative splicing factor Rbfox1 is selectively down-regulated in the accumbens of Type III-Nrg1 heterozygous mice. These findings provide evidence that deficient Nrg1 signaling alters maturational changes in the accumbens. Such alterations are likely to influence the establishment and maturation of glutamatergic transmission in the accumbens."},{"label":"dcterms.available","value":"2017-09-20T16:50:33Z"},{"label":"dcterms.contributor","value":"Maffei, Arianna."},{"label":"dcterms.creator","value":"Obiorah, Ifeanyi Vincent"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:50:33Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:50:33Z"},{"label":"dcterms.description","value":"Department of Molecular and Cellular Pharmacology."},{"label":"dcterms.extent","value":"99 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/76523"},{"label":"dcterms.issued","value":"2015-08-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:50:33Z (GMT). No. of bitstreams: 1\nObiorah_grad.sunysb_0771E_11822.pdf: 8538582 bytes, checksum: ecdd75b9235b24528b558ef4b1cac57b (MD5)\n  Previous issue date: 2014"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Neurosciences"},{"label":"dcterms.title","value":"The Role of Type III-Nrg1 signaling in excitatory transmission in the nucleus accumbens"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/13%2F64%2F30%2F136430957995856245164919360817588668278/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/13%2F64%2F30%2F136430957995856245164919360817588668278","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}