- Title
- Channelrhodopsin-assisted circuit mapping of medial amygdaloid connectivity to the paraventricular nucleus of the hypothalamus
- Creator
- Adams, Cameron Darcy
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2018
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Understanding how the brain is connected is an important first step if we are to successfully treat its conditions. Currently, much of what we know about the brain connectome has been discovered through neuroanatomical tracing studies. This approach however, lacks functionality in that we cannot determine the physiological consequences of manipulating a given pathway or its overall necessity to a specific behavioural outcome. Dysregulated social and emotional functioning, including hypothalamic-pituitary-adrenal (HPA) axis responses, are cardinal features of depressive disorders. Not surprisingly, HPA axis activity is tightly regulated by limbic structures including the medial (MeA) and central amygdala (CeA) which act to increase hypothalamic neuroendocrine output. The lack of direct connectivity between these amygdaloid structures and the neuroendocrine hypothalamus has led to suggestions the MeA and CeA mediate HPA axis responses to stress via indirect relays. While historically, the CeA has received considerable attention in regards to HPA axis regulation, both traditional and modern tracing techniques provide anatomical evidence of direct MeA to hypothalamic neuroendocrine connectivity. At this time however, functional evidence supporting this connection is lacking. Fortunately, recent advances in technology now allows for a functional assessment of individual pathways within the brain connectome. Through the application of optogenetics, the primary goal of this thesis is to investigate the functional characteristics of a direct MeA to neuroendocrine hypothalamus projection. In this regard, I demonstrate the capacity of the MeA to drive stress neuroendocrine responses through direct, functional projections to the hypothalamus. Moreover, that a group of MeA neurons, which may be derived from a neuroendocrine lineage, provide direct glutamatergic input to corticotropin-releasing factor (CRF) neurons, which sit at the apex of the HPA axis. Together, these results suggest therapeutically targeting the MeA, as opposed to the CeA, may prove to be more successful in the treatment of mood related disorders.
- Subject
- amygdala; CRF; HPA Axis; optogenetics; PVN; stress
- Identifier
- http://hdl.handle.net/1959.13/1387401
- Identifier
- uon:32599
- Rights
- Copyright 2018 Cameron Darcy Adams
- Language
- eng
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| Thumbnail | File | Description | Size | Format | |||
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| View Details Download | ATTACHMENT01 | Thesis | 2 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 291 KB | Adobe Acrobat PDF | View Details Download |