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You searched for +publisher:"Duke University" +contributor:("WEST, ANNE E"). Showing records 1 – 2 of 2 total matches.

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Duke University

1. WIJAYATUNGE, RANJULA. The H3K27 Histone Demethylase Kdm6b (Jmjd3) is Induced by Neuronal Activity and Contributes to Neuronal Survival and Differentiation .

Degree: 2012, Duke University

Changes in gene transcription driven by the activation of intracellular calcium signaling pathways play an important role in neural development and plasticity. A growing body of evidence suggests that stimulus-driven modulation of histone modifications play an important role in the regulation of neuronal activity-regulated gene transcription. However, the histone modifying enzymes that are targets of activity-regulated signaling cascades in neurons remain to be identified. The histone demethylases (HDMs) are a large family of enzymes that have selective catalytic activity against specific sites of histone methylation. To identify HDMs that may be important for activity-regulated gene transcription in neurons, we induced seizures in mice and screened for HDMs whose expression is induced in the hippocampus. Among the few HDMs that changed expression, Kdm6b showed the highest induction. Kdm6B is a histone H3K27-specific HDM whose enzymatic activity leads to transcriptionally permissive chromatin environments. In situ hybridization analysis revealed that Kdm6b is highly induced in post-mitotic neurons of the dentate gyrus region of the hippocampus. We can recapitulate the activity-dependent induction of Kdm6b expression in cultured hippocampal neurons by application of Bicuculline, a GABAA receptor antagonist that leads to synaptic NMDA receptor activation and calcium influx. Kdm6b expression is also induced following application of BDNF, a neurotrophic factor that is upregulated in the seized hippocampus. To investigate possible functions of Kdm6b in neuronal development, we performed in situ hybridization analysis that allows for the identification of regions with high Kdm6b expression that could be sites of potential function in the developing mouse brain. We found high levels of Kdm6b expression in the inner layer of the external granule layer of the cerebellum, a region where pre-migratory immature neurons reside and a site of significant apoptosis. On the basis of this data and the fact that intracellular calcium signaling arising from synaptic firing supports neuronal survival, we explored the necessity for Kdm6b in the survival of cultured cerebellar granule cells. Knock down of Kdm6b by RNAi increases cell death, demonstrating that Kdm6b contributes to neuronal survival. Ongoing experiments are addressing the role of Kdm6b in neuronal differentiation. Overall these data raise the possibility that stimulus-dependent regulation of Kdm6b, and perhaps regulation of H3K27 methylation mediated by Kdm6b, may contribute to the regulation of gene expression in neurons and thus to their proper development and plasticity. Advisors/Committee Members: WEST, ANNE E (advisor).

Subjects/Keywords: Neurosciences; Differentiation; Histone demethylases; Kdm6b; Survival

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

WIJAYATUNGE, R. (2012). The H3K27 Histone Demethylase Kdm6b (Jmjd3) is Induced by Neuronal Activity and Contributes to Neuronal Survival and Differentiation . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/5577

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

WIJAYATUNGE, RANJULA. “The H3K27 Histone Demethylase Kdm6b (Jmjd3) is Induced by Neuronal Activity and Contributes to Neuronal Survival and Differentiation .” 2012. Thesis, Duke University. Accessed March 20, 2019. http://hdl.handle.net/10161/5577.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

WIJAYATUNGE, RANJULA. “The H3K27 Histone Demethylase Kdm6b (Jmjd3) is Induced by Neuronal Activity and Contributes to Neuronal Survival and Differentiation .” 2012. Web. 20 Mar 2019.

Vancouver:

WIJAYATUNGE R. The H3K27 Histone Demethylase Kdm6b (Jmjd3) is Induced by Neuronal Activity and Contributes to Neuronal Survival and Differentiation . [Internet] [Thesis]. Duke University; 2012. [cited 2019 Mar 20]. Available from: http://hdl.handle.net/10161/5577.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

WIJAYATUNGE R. The H3K27 Histone Demethylase Kdm6b (Jmjd3) is Induced by Neuronal Activity and Contributes to Neuronal Survival and Differentiation . [Thesis]. Duke University; 2012. Available from: http://hdl.handle.net/10161/5577

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Duke University

2. Lee, Ming-Chia. Input-Specific Metaplasticity by a Local Switch in NMDA Receptors .

Degree: 2009, Duke University

At excitatory synapses, NMDAR-mediated synaptic plasticity occurs in response to activity inputs by modifying synaptic strength. While comprehensive studies have been focused on the induction and expression mechanisms underlying synaptic plasticity, it is less clear whether and how synaptic plasticity itself can be subjected to regulations. The presence of "plasticity of plasticity", or meta-plasticity, has been proposed as an essential mechanism to ensure a proper working range of plasticity, which may also offer an additional layer of information storage capacity. However, it remains elusive whether and how meta-plasticity occurs at single synapses and what molecular substrates are locally utilized. Here, I develop systems allowing for sustained alterations of individual synaptic inputs. By implementing a history of inactivity at single synapses, I demonstrate that individual synaptic inputs control synaptic molecular composition homosynaptically, while allowing heterosynaptic integration along dendrites. Furthermore, I report that subunit-specific regulation of NMDARs at single synapses mediates a novel form of input-specific metaplasticity. Prolonged suppression of synaptic releases at single synapses enhances synaptic NMDAR-mediated currents and increases the number of functional NMDARs containing NR2B. Interestingly, synaptic NMDAR composition is adjusted by spontaneous glutamate release rather than evoked activity. I also demonstrate that inactivated synapses with more NMDARs containing NR2B acquire a lower induction threshold for long-term synaptic potentiation. Together, these results suggest that at single synapses, spontaneous release primes the synapse by modifying its synaptic state with specific molecular compositions, which in turn determine the synaptic gain in an input-specific manner. Advisors/Committee Members: Ehlers, Michael D (advisor), West, Anne E (advisor).

Subjects/Keywords: Biology, Neuroscience; Input; specific; LTP; Metaplasticity; NMDA receptors; Plasticity threshold

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Lee, M. (2009). Input-Specific Metaplasticity by a Local Switch in NMDA Receptors . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/1148

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Lee, Ming-Chia. “Input-Specific Metaplasticity by a Local Switch in NMDA Receptors .” 2009. Thesis, Duke University. Accessed March 20, 2019. http://hdl.handle.net/10161/1148.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Lee, Ming-Chia. “Input-Specific Metaplasticity by a Local Switch in NMDA Receptors .” 2009. Web. 20 Mar 2019.

Vancouver:

Lee M. Input-Specific Metaplasticity by a Local Switch in NMDA Receptors . [Internet] [Thesis]. Duke University; 2009. [cited 2019 Mar 20]. Available from: http://hdl.handle.net/10161/1148.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lee M. Input-Specific Metaplasticity by a Local Switch in NMDA Receptors . [Thesis]. Duke University; 2009. Available from: http://hdl.handle.net/10161/1148

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.