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Dissertation
Astrocyte modulation of synaptic plasticity mediated by activity-dependent Sonic hedgehog signaling
Doctor of Philosophy (Ph.D.), Drexel University
Mar 2025
DOI:
https://doi.org/10.17918/00010891
Abstract
The ability of neural circuits to modify their structure and function in response to experience requires coordinated action of multiple cell types. While neurons are the primary mediators of information processing, astrocytes are emerging as essential partners in experience-dependent plasticity. However, the molecular mechanisms that couple neuronal activity to changes in astrocyte function remain poorly understood. This thesis identifies Sonic hedgehog (Shh) signaling as a key pathway through which neurons communicate with astrocytes to facilitate activity-dependent circuit modification. This thesis demonstrates for the first time that Shh signaling is dynamically regulated by neuronal activity in vivo. Through regulation of synapse-modifying molecules like Hevin and SPARC, activity-dependent Shh enables astrocytes to modify synapses in response to novel experience. This work also identified Shh-and-activity-dependent regulation of ETNPPL, a lipid metabolism protein, knockdown of which disrupted astrocyte morphology and synapse interaction. Together, these findings establish Shh as a mechanism through which neurons recruit astrocyte participation to facilitate experience-dependent plasticity.
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Details
- Title
- Astrocyte modulation of synaptic plasticity mediated by activity-dependent Sonic hedgehog signaling
- Creators
- Anh Duc Le
- Contributors
- Anna Denise R. Garcia (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 163 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 991022040961404721