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.
| Date of Award | 2019 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Matthew Grubb (Supervisor), Jonathan Mill (Supervisor) & Chloe Wong (Supervisor) |