Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.769966
Title: Characterising dopaminergic plasticity in the mouse olfactory bulb
Author: Byrne, Darren John
ISNI:       0000 0004 7660 365X
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
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Abstract:
Experience can shape the brain through multiple interacting forms of neuronal plasticity. In the mouse olfactory bulb, a heterogenous population of dopaminergic neurons is known to be particularly plastic, regulating their gene expression and lifelong generation in an activity-dependent manner. However, how their electrophysiological function can change is not well understood. This thesis aimed to understand how olfactory bulb dopaminergic neurons respond functionally following perturbation of odour experience. I live labelled olfactory bulb dopaminergic neurons using the DATIREScre transgenic mouse. I characterised the labelled population at postnatal day (P)28, showing that the majority of neurons are dopaminergic. Approximately 22% of the labelled population is calretinin-positive, which can be distinguished from the dopaminergic population by immunohistochemistry and electrophysiology. I used an odour deprivation manipulation, unilateral naris occlusion, for 1 and 3 days to study experience-dependent plasticity in the labelled neurons. I show with immunohistochemistry that the activity of these neurons is reduced and there is downregulation of the dopamine-synthesising enzyme, tyrosine hydroxylase, as quickly as 1 day after occlusion. To investigate electrophysiological functional plasticity, I used acute slice electrophysiology to study a subpopulation of olfactory bulb dopaminergic neurons that lack an axon. I demonstrate that the firing properties of these neurons are not affected by these durations of occlusion. However, I show that after 3 days of occlusion there is a significant increase in the sag potential, medium afterhyperpolarisation and amplitude and charge of mini excitatory postsynaptic currents in anaxonic olfactory bulb dopaminergic neurons. I investigated GABAA-mediated auto-inhibition in both subpopulations of olfactory bulb dopaminergic neurons - axonic and anaxonic. I show that, unlike presumed anaxonic cells, presumed axonic dopaminergic neurons do not have auto-inhibition, except following pharmacological enhancement of L-type calcium channels. Whilst studying auto-inhibition, I found a calcium-dependent current that was present in the majority of presumed axonic dopaminergic neurons and only a minority of the presumed anaxonic subpopulation. This work provides further insight into experience-dependent plasticity of olfactory bulb dopaminergic neurons and reveals important functional differences between subtypes of this population.
Supervisor: Grubb, Matthew Stuart ; Mill, Jonathan ; Wong, Chloe Chung Yi Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.769966  DOI: Not available
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