| Dissertation |
Thesis (M.Sc.) --NUI, 2016 at Department of Anatomy & Neuroscience, UCC. |
| Summary |
The growth hormone secretagogue 1α (GHS-R1α) receptor, is a G-protein coupled receptor (GPCR), which is highly expressed in both the periphery and the brain. Its endogenous ligand, ghrelin, is produced in the gut and activates its receptor, also called the ghrelin receptor, to release growth hormone from the pituitary and to centrally regulate appetite and food intake after passing the blood-brain-barrier. Ghrelin-mediated activation of the GHS-R1α receptor also mediates multiple additional functions within the periphery including, gastrointestinal motility, adiposity, glucose and lipid metabolism. However, the ghrelinergic system is also implicated in additional behaviours, including reward and motivation, learning and the stress response, due to the ubiquitous expression of the GHS-R1α receptor in areas such as the ventral tegmental area, nucleus accumbens, hippocampus and the amygdala. Ghrelin has been identified to participate in many critical functions within the hippocampus, including neurogenesis, pattern separation, synaptic plasticity, improving cognition and promoting long-term potentiation. Indeed, oligomerization between the GHS-R1α receptor and other GPCRs of the monoamine family including the dopamine 1 receptor (D1), the dopamine 2 receptor (D2), and the serotonin 2C receptor (5-HT2C), has been identified within the hippocampus. The research conducted in this thesis aims to understand the functional relevance of the recently identified cross talk between the ghrelinergic, dopaminergic and serotoninergic systems. Via electrophysiological measurements, using the multi-electrode array system, we demonstrated for the first time interaction between GHS-R1α receptor activation and 5-HT2C and D1 receptor signalling on basal synaptic transmission in the hippocampus. Furthermore, we investigated the physiological relevance of this crosstalk in the formation of associative fear memory in vivo. These results encourage further studies investigating the functional consequences of the interaction between the GHS-R1α receptor and the monoamine neurotransmitter systems of dopamine and serotonin in hippocampal-dependent behaviour and other extra-hypothalamic GHS-R1α receptor-dependent behaviour. Understanding the changes induced by dimerization, will better improve our ability to understand and treat disorders associated with fear memory such as post-traumatic stress disorder through poly-drug treatments. |
| Subject |
Neurosciences.
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Brain.
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| Collection |
Theses Masters (Research)
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Theses Anatomy and Neuroscience Department
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| Description |
105 pages ; 30 cm. |
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