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http://hdl.handle.net/11375/29081
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DC Field | Value | Language |
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dc.contributor.advisor | Gillespie, Deda C | - |
dc.contributor.author | Simon, Shane Joseph | - |
dc.date.accessioned | 2023-10-17T14:34:58Z | - |
dc.date.available | 2023-10-17T14:34:58Z | - |
dc.date.issued | 2023 | - |
dc.identifier.uri | http://hdl.handle.net/11375/29081 | - |
dc.description.abstract | High precision is critical for normal neural circuit function, but that precision is not innate. The location, strength, and number of inputs in a neural circuit are modified in early postnatal development in a process called refinement. The refinement of long-range excitatory projections is well-known, but less is known about the refinement of long-range inhibitory projections. What we do know about inhibitory projection refinement comes from the glycinergic medial nucleus to the trapezoid body to lateral superior olive (MNTB-LSO) projection of the auditory brainstem. During early postnatal life, the MNTB-LSO projection undergoes morphological and physiological refinement. Notably, the MNTB-LSO projection transiently expresses vesicular glutamate transporter 3 (VGLUT3) and synaptotagmin 1 (Syt1), transiently releases glutamate, and undergoes glutamate-dependent refinement. However, it remains uncertain whether glutamate release is specific to the auditory brainstem or could be a more general phenomenon of inhibitory projections. To shed light on this question, I investigated another inhibitory projection of the hindbrain, the GABAergic Purkinje projection of the cerebellum. The Purkinje projection shares key characteristics with the MNTB-LSO projection, including its inhibitory nature, location in the hindbrain, obvious topographic organization, heterogeneity of the target cells, and expression of VGLUT3 transcript and protein. In this thesis, I sought to determine: 1) whether the expression profile of VGLUT3 and Syt1 in the Purkinje projection matches that of the MNTB-LSO projection, and whether the Purkinje projection also releases glutamate, 2) whether the expression profile of synaptic vesicle protein 2 (SV2) isoforms, SV2B and SV2C, matches the expression profile of other synaptic vesicle proteins in the Purkinje and MNTB-LSO projection, and 3) whether the Purkinje projection undergoes postnatal morphological refinement like the MNTB-LSO projection. I found that like the MNTB-LSO projection, the Purkinje projection transiently expresses VGLUT3 and Syt1, releases glutamate in early postnatal life, and may undergo morphological refinement. | en_US |
dc.language.iso | en | en_US |
dc.subject | Purkinje | en_US |
dc.subject | refinement | en_US |
dc.subject | inhibition | en_US |
dc.subject | cerebellum | en_US |
dc.subject | VGLUT3 | en_US |
dc.subject | neural circuits | en_US |
dc.subject | axon | en_US |
dc.subject | development | en_US |
dc.title | On the development of inhibitory projection neurons | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Health Sciences | en_US |
dc.description.degreetype | Dissertation | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
dc.description.layabstract | Everything you do, whether it be playing your favorite sport or begrudgingly reading this thesis, requires neural circuits, which are the basic functional unit of the nervous system. How neurons are wired together is crucial for their role in executing a task. But how these neurons fine-tune their connections – in a process called refinement, by getting the right connections to the right location, of the right strength, and of the right number – is an open-ended question in neuroscience. Refinement is more well-studied in excitatory projection neurons, but we know very little about how refinement occurs in inhibitory projection neurons. I compare some of the unusual characteristics of what we do know about inhibitory refinement in the auditory brainstem to another famous projection of the hindbrain, the Purkinje projection. Understanding more about the refinement of inhibitory projections gives key insights into how neural circuits function and how they facilitate complex behaviours. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Simon_Shane_J_202309_PhD.pdf | 5.67 MB | Adobe PDF | View/Open |
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