Characterization and Behavioural Relevance of the A11 Hypothalamospinal Dopaminergic System in the Mouse
Abstract
The A11 region, located in the posterior hypothalamus, has been identified in several species including rats, mice, cats, monkeys, zebrafish, and humans. It has been suggested to be the primary source of dopaminergic projections to the spinal cord and it may contribute to the control of pain, spinal locomotor network modulation, restless leg syndrome, and cataplexy. However, it remains an understudied dopaminergic nucleus within the brain and we lack understanding of the functional role of this nucleus. My thesis aims to identify and characterize the enzymatic phenotype of A11, its role in locomotor activity and possible connections to other locomotor areas within the brain. I hypothesized that A11 neurons project to the spinal cord and contain the full set of enzymes required for dopamine synthesis. Using immunohistochemistry combined with virus transfection in TH-IRES-Cre mice, I show that A11 neurons (1) directly project to the spinal cord, (2) express tyrosine hydroxylase, as well as AADC, confirming that A11 is dopaminergic, (3) contain vesicular monoamine transporter 2 necessary for packaging DA into vessels but (4) lack the dopamine transporter. I conclude that A11 neurons contain the full complement of enzymes to produce and release dopamine and the lack of DAT could lead to prolonged DA actions within the spinal cord. Furthermore, I hypothesized that the A11 region forms a parallel dopamine-based pathway for movement initiation and control. Using optogenetics, I found that photostimulation of A11 (1) initiates and modulates locomotion in freely moving mice (2) independent of the locus coeruleus. Lastly, I investigate possible direct dopaminergic connections to well known locomotor areas in the brainstem, which could form a parallel pathway to the nigrostriatal system. I found projections from A11 to the medullary reticular formation but not to the mesencephalic locomotor region. Together the data in this thesis reveal a new role for the A11 region in movement control in the freely moving mouse.
Description
Keywords
Neuroscience
Citation
Koblinger, K. (2017). Characterization and Behavioural Relevance of the A11 Hypothalamospinal Dopaminergic System in the Mouse (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25259