Morphological and Activity-Dependent Effects of Astrocyte Activation in the Orbitofrontal Cortex
| dc.contributor.advisor | Borgland, Stephanie | |
| dc.contributor.author | Sobey, Marissa | |
| dc.contributor.committeemember | Kurrasch, Deborah | |
| dc.contributor.committeemember | Bains, Jaideep | |
| dc.contributor.committeemember | Gordon, Grant | |
| dc.date | 2022-11 | |
| dc.date.accessioned | 2022-09-29T20:58:34Z | |
| dc.date.available | 2022-09-29T20:58:34Z | |
| dc.date.issued | 2022-09 | |
| dc.description.abstract | Astrocytes, the most abundant glial cell in the central nervous system (CNS), have significant roles in supplying energetic substrates to neurons, regulating blood brain barrier (BBB) permeability, homeostasis of ions and pH to neurons in the tripartite synapse. Much remains unknown about astrocytes due to the limitations of current tools to visualize and manipulate astrocyte activity. To understand astrocyte physiology and pathophysiology, we need methods to visualize and specifically assess the activity of astrocytes. A recent astrocyte promoter, gfaABC1D, may provide better astrocyte specificity and transduction efficiency in the cortex. S100B is a calcium-binding glycoprotein only expressed in the soma of astrocytes also can be used as a marker for astrocytes. To activate cortical astrocytes, we targeted excitatory Designer Receptors Exclusively Activated by Designer Drugs (hM3Dq DREADDs) to astrocytes of the orbitofrontal cortex (OFC), a region involved in decision making and injected the DREADD-specific, brain penetrant ligand, DCZ. I hypothesize that using a combination approach of S100B, and gfaABC1D-tagged DREADD virus will successfully label and activate astrocytes in the lateral OFC (LOFC), whilst not indirectly influencing neuronal activity (measured by cFos). This thesis used a novel IMARIS 3D visualization method to visualize astrocytes and the colocalization of the DREADD-reporter in astrocytes. The result suggests that there are more astrocytes in the LOFC compared to the medial (MOFC), independent of DCZ administration. There is intraregional heterogeneity between the LOFC and the MOFC. The gfaABC1D-DREADD virus successfully transfected astrocytes in LOFC. There was no increase in cFos intensity in NeuN cells in the LOFC or the MOFC, suggesting that activation of Gq-DREADDs in astrocytes was not sufficient to affect neuronal activation. Future research should address the calcium activity response to DCZ on excitatory DREADDS in astrocytes in-vitro. This thesis offers an acute method to assess astrocytes in the cortex to further be used in a chronic model to induce inflammation, to better understand cortical reward system inflammation seen in addiction and obesity. | en_US |
| dc.identifier.citation | Sobey, M. (2022). Morphological and activity-dependent effects of astrocyte activation in the orbitofrontal cortex (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1880/115326 | |
| dc.identifier.uri | https://dx.doi.org/10.11575/PRISM/40332 | |
| dc.language.iso | eng | en_US |
| dc.publisher.faculty | Cumming School of Medicine | en_US |
| dc.publisher.institution | University of Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | en_US |
| dc.subject.classification | Neuroscience | en_US |
| dc.title | Morphological and Activity-Dependent Effects of Astrocyte Activation in the Orbitofrontal Cortex | en_US |
| dc.type | master thesis | en_US |
| thesis.degree.discipline | Medicine – Neuroscience | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Master of Science (MSc) | en_US |
| ucalgary.item.requestcopy | true | en_US |