Abstract
The mammalian dopaminergic system plays a crucial role in the execution of many key brain functions, and has been extensively researched over past decades. The majority of dopamine neurons are primarily located within the midbrain, but also produce projections to vast proportions of the central nervous system. Little is known about which dopamine neurons project to different parts of the striatum, therefore this study aimed to define dopamine projections to the dorso-medial and ventro-lateral striatum, while also testing the hypothesis that there are differential characteristics and functionalities between diverse heterogeneous dopamine subpopulations. Neurons were traced retrogradely with Cholera Toxin B and tested for immunoreactivity to Tyrosine Hydroxylase, calbindin, calretinin, Aldh1a1 and Sox6. Analysis showed a significant proportion of dopamine neurons projecting to ventral lateral striatum express Sox6 and Aldh1a1 (70% and 50% respectively), but express little to no calretinin (<10%), whereas those projecting to the dorsal medial striatum express slightly higher proportions of calretinin (<20%). The data also show differences in projection patterns for dopamine neurons originating in different sites within the midbrain, possibly affecting functionality as a consequence. Whilst both populations originate in similar regions of the midbrain, a higher percentage of cell bodies of DMS projecting dopamine neurons are located in the medial SNC whereas VLS projecting dopamine neurons are in the lateral VTA and the most dorsal parts of the SNc. These results support a theory of dopaminergic heterogeneity.Dopamine neurons are some of the most vulnerable in many neurological disorders, in particular Parkinson’s Disease, which is incredibly prevalent in today’s ageing society, and for which there is currently no cure. This study provides some insight into ways to delineate
12 different types of dopamine neurons that may help to better define the vulnerable populations for future therapy, based on the distinct protein expressions of the striatal projections.
| Date of Award | 20 Jun 2023 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Elizabeth Warburton (Supervisor) & Paul Dodson (Supervisor) |