The distribution of Dopamine Receptors in the Mesencephalic Locomotor Region and colocalization with inhibitory and excitatory cell types

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dc.contributor.advisorWhelan, Patrick
dc.contributor.authorDi Vito, Stephanie
dc.contributor.committeememberWilson, Richard
dc.contributor.committeememberBorgland, Stephanie
dc.contributor.committeememberLohman, Alex
dc.date2024-05
dc.date.accessioned2024-03-21T16:40:08Z
dc.date.available2024-03-21T16:40:08Z
dc.date.issued2024-03-20
dc.description.abstractThe dopaminergic (DA) control of motor function has for many decades been thought to be indirect via substantia nigra pars compacta (SNc) projections to the striatum. DA interaction with dopamine D1 or D2 -receptor (D1R or D2R) expressing cells in the striatum leads to locomotion via disinhibition of Mesencephalic Locomotor region (MLR) neurons. The MLR is known to be a key centre for the control of locomotion. It comprises the cuneiform nucleus (CnF) and pedunculopontine nucleus (PPN). These regions are heterogeneous and show differential effects on locomotion following stimulation of either glutamatergic or GABAergic cells. The MLR receives predominantly inhibitory input from the basal ganglia. Recently, our lab discovered that a dopaminergic nucleus within the medial zona incerta (mZI); the A13, projects to the MLR. Direct dopaminergic projections that modulate locomotion, from the SNc to the MLR, have also been identified in lampreys and rats. This suggests at least two direct dopaminergic control pathways to the MLR that lie parallel to the canonical nigrostriatal DA pathway and modulate motor control. However, it is not well understood how dopamine receptors are distributed across cellular subtypes in the MLR. In this thesis I used adult C57BL/6 male and female mice to address this gap. RNAscope® was performed to determine the distribution of DA receptor mRNA on vGLUT2 and vGAT neurons within the PPN and CnF. Overall, D2+5R were the highest expressing subtypes of DARs, while D1,3, and 4R were sparsely expressed. There were no significant differences in D1-5R expression between the PPN and CnF. D5R cells showed colocalization with cells expressing vGLUT2 mRNA, while D2R had significant subpopulations of cells expressing both vGAT and vGLUT2 mRNA. My thesis suggests that DA modulation of MLR neurons are predominantly D2R mediated, and dopamine may play a role in opposing behaviours, due to D2R expression on glutamatergic and GABAergic cells. Further investigation is needed to determine the functional role of dopamine receptors in the MLR and upstream nuclei (A13, SNc, or both) contributing to dopaminergic modulation of the MLR.
dc.identifier.citationDi Vito, S. (2024). The distribution of dopamine receptors in the mesencephalic locomotor region and colocalization with inhibitory and excitatory cell types (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/118311
dc.identifier.urihttps://doi.org/10.11575/PRISM/43154
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectMesencephalic Locomotor Region
dc.subjectDopamine Receptors
dc.subjectRNAscope
dc.subject.classificationNeuroscience
dc.titleThe distribution of Dopamine Receptors in the Mesencephalic Locomotor Region and colocalization with inhibitory and excitatory cell types
dc.typemaster thesis
thesis.degree.disciplineMedicine – Neuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.thesis.accesssetbystudentI require a thesis withhold – I need to delay the release of my thesis due to a patent application, and other reasons outlined in the link above. I have/will need to submit a thesis withhold application.
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