Dean, Camin

[["dc.bibliographiccitation.artnumber","eaav1483"],["dc.bibliographiccitation.issue","6422"],["dc.bibliographiccitation.journal","Science (New York, N.Y.)"],["dc.bibliographiccitation.volume","363"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Ramachandran, Binu"],["dc.contributor.author","Ahmed, Saheeb"],["dc.contributor.author","Benito, Eva"],["dc.contributor.author","Shinoda, Yo"],["dc.contributor.author","Nitzan, Noam"],["dc.contributor.author","Heukamp, Alina"],["dc.contributor.author","Rannio, Sabine"],["dc.contributor.author","Martens, Henrik"],["dc.contributor.author","Barth, Jonas"],["dc.contributor.author","Burk, Katja"],["dc.contributor.author","Wang, Yu Tian"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Dean, Camin"],["dc.date.accessioned","2019-07-31T13:02:46Z"],["dc.date.available","2019-07-31T13:02:46Z"],["dc.date.issued","2019"],["dc.description.abstract","Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting."],["dc.identifier.doi","10.1126/science.aav1483"],["dc.identifier.pmid","30545844"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62245"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1095-9203"],["dc.relation.issn","0036-8075"],["dc.relation.issn","1095-9203"],["dc.title","Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3572"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","3584"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Benito-Garagorri, Eva"],["dc.contributor.author","Urbanke, Hendrik"],["dc.contributor.author","Ramachandran, Binu"],["dc.contributor.author","Barth, Jonas"],["dc.contributor.author","Haider, Rashi"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Jain, Gaurav"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Navarro-Sala, Magdalena"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Luehrmann, Reinhard"],["dc.contributor.author","Dean, Camin"],["dc.contributor.author","Fischer, Andre"],["dc.date.accessioned","2017-09-07T11:43:34Z"],["dc.date.available","2017-09-07T11:43:34Z"],["dc.date.issued","2015"],["dc.description.abstract","Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer's disease (AD). Effective therapies for these diseases are lacking. Here, we evaluated mouse models of age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity in the brain and peripheral organs. We determined that aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region as the result of epigenetic-dependent alterations in gene expression. In both amyloid and aging models, inflammation was associated with increased gene expression linked to a subset of transcription factors, while plasticity gene deregulation was differentially mediated. Amyloid pathology impaired histone acetylation and decreased expression of plasticity genes, while aging altered H4K12 acetylation-linked differential splicing at the intron-exon junction in neurons, but not nonneuronal cells. Furthermore, oral administration of the clinically approved histone deacetylase inhibitor vorinostat not only restored spatial memory, but also exerted antiinflammatory action and reinstated epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This study provides a systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and suggests that histone deacetylase inhibitors should be further explored as a cost-effective therapeutic strategy against age-associated cognitive decline."],["dc.identifier.doi","10.1172/JCI79942"],["dc.identifier.gro","3141833"],["dc.identifier.isi","000362303600031"],["dc.identifier.pmid","26280576"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1579"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1558-8238"],["dc.relation.issn","0021-9738"],["dc.title","HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","15878"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Hurtado-Zavala, Joaquin I."],["dc.contributor.author","Ramachandran, Binu"],["dc.contributor.author","Ahmed, Saheeb"],["dc.contributor.author","Halder, Rashi"],["dc.contributor.author","Bolleyer, Christiane"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Stahlberg, Markus A."],["dc.contributor.author","Wagener, Robin J."],["dc.contributor.author","Anderson, Kristin"],["dc.contributor.author","Drenan, Ryan M."],["dc.contributor.author","Lester, Henry A."],["dc.contributor.author","Miwa, Julie M."],["dc.contributor.author","Staiger, Jochen F."],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Dean, Camin"],["dc.date.accessioned","2018-04-23T11:47:16Z"],["dc.date.available","2018-04-23T11:47:16Z"],["dc.date.issued","2017"],["dc.description.abstract","TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine—via α2β2-containing nicotinic receptors—to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity."],["dc.identifier.doi","10.1038/ncomms15878"],["dc.identifier.gro","3142196"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14910"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13316"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","149"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of general physiology"],["dc.bibliographiccitation.lastpage","170"],["dc.bibliographiccitation.volume","149"],["dc.contributor.author","Wolfes, Anne C."],["dc.contributor.author","Ahmed, Saheeb"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Stahlberg, Markus A."],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Magruder, Daniel S."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Dean, Camin"],["dc.date.accessioned","2019-07-09T11:43:25Z"],["dc.date.available","2019-07-09T11:43:25Z"],["dc.date.issued","2017"],["dc.description.abstract","Interactions between astrocytes and neurons rely on the release and uptake of glial and neuronal molecules. But whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures. This method is superior to other monocultures in terms of astrocyte morphology, mRNA expression profile, protein expression of cell maturity markers, and Ca(2+) fluctuations: In astrocytes transduced with GFAP promoter-driven Lck-GCaMP3, spontaneous Ca(2+) events in distinct domains (somata, branchlets, and microdomains) are similar to those in astrocytes co-cultured with other glia and neurons but unlike Ca(2+) events in astrocytes prepared using the McCarthy and de Vellis (MD) method and immunopanned (IP) astrocytes. We identify two distinct populations of constitutively recycling vesicles (harboring either VAMP2 or SYT7) specifically in branchlets of cultured stellate astrocytes. SYT7 is developmentally regulated in these astrocytes, and we observe significantly fewer synapses in wild-type mouse neurons grown on Syt7(-/-) astrocytes. SYT7 may thus be involved in trafficking or releasing synaptogenic factors. In summary, our novel method yields stellate astrocyte monocultures that can be used to study Ca(2+) signaling and vesicle recycling and dynamics in astrocytic processes."],["dc.description.abstract","whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures. This method is superior to other monocultures in terms of astrocyte morphology, mRNA expression profile, protein expression of cell maturity markers, and Ca2+ fluctuations: In astrocytes transduced with GFAP promoter–driven Lck-GCaMP3, spontaneous Ca2+ events in distinct domains (somata, branchlets, and microdomains) are similar to those in astrocytes co-cultured with other glia and neurons but unlike Ca2+ events in astrocytes prepared using the McCarthy and de Vellis (MD) method and immunopanned (IP) astrocytes. We identify two distinct populations of constitutively recycling vesicles (harboring either VAMP2 or SYT7) specifically in branchlets of cultured stellate astrocytes. SYT7 is developmentally regulated in these astrocytes, and we observe significantly fewer synapses in wild-type mouse neurons grown on Syt7−/− astrocytes. SYT7 may thus be involved in trafficking or releasing synaptogenic factors. In summary, our novel method yields stellate astrocyte monocultures that can be used to study Ca2+ signaling and vesicle recycling and dynamics in astrocytic processes."],["dc.identifier.doi","10.1085/jgp.201611607"],["dc.identifier.pmid","27908976"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14524"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58885"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/260916/EU//SYT ACTIVITY"],["dc.relation.issn","1540-7748"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject.ddc","612"],["dc.title","A novel method for culturing stellate astrocytes reveals spatially distinct Ca2+ signaling and vesicle recycling in astrocytic processes."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1087"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cerebral Cortex"],["dc.bibliographiccitation.lastpage","1104"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Burk, Katja"],["dc.contributor.author","Ramachandran, Binu"],["dc.contributor.author","Ahmed, Saheeb"],["dc.contributor.author","Hurtado-Zavala, Joaquin I"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Benito, Eva"],["dc.contributor.author","Faram, Ruth"],["dc.contributor.author","Ahmad, Hamid"],["dc.contributor.author","Swaminathan, Aarti"],["dc.contributor.author","McIlhinney, Jeffrey"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Perestenko, Pavel"],["dc.contributor.author","Dean, Camin"],["dc.date.accessioned","2018-01-09T14:34:30Z"],["dc.date.available","2018-01-09T14:34:30Z"],["dc.date.issued","2017"],["dc.description.abstract","Dendritic spines compartmentalize information in the brain, and their morphological characteristics are thought to underly synaptic plasticity. Here we identify copine-6 as a novel modulator of dendritic spine morphology. We found that brain-derived neurotrophic factor (BDNF) - a molecule essential for long-term potentiation of synaptic strength - upregulated and recruited copine-6 to dendritic spines in hippocampal neurons. Overexpression of copine-6 increased mushroom spine number and decreased filopodia number, while copine-6 knockdown had the opposite effect and dramatically increased the number of filopodia, which lacked PSD95. Functionally, manipulation of post-synaptic copine-6 levels affected miniature excitatory post-synaptic current (mEPSC) kinetics and evoked synaptic vesicle recycling in contacting boutons, and post-synaptic knockdown of copine-6 reduced hippocampal LTP and increased LTD. Mechanistically, copine-6 promotes BDNF-TrkB signaling and recycling of activated TrkB receptors back to the plasma membrane surface, and is necessary for BDNF-induced increases in mushroom spines in hippocampal neurons. Thus copine-6 regulates BDNF-dependent changes in dendritic spine morphology to promote synaptic plasticity."],["dc.identifier.doi","10.1093/cercor/bhx009"],["dc.identifier.pmid","28158493"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11602"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1460-2199"],["dc.title","Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]