Abstract
The mesencephalic locomotor region (MLR) is an important integrative area for the initiation and modulation of locomotion. Recently it has been realized that dopamine (DA) projections from the substantia nigra pars compacta project to the MLR. Here we explore DA projections from an area of the medial zona incerta (ZI) known for its role in motor control onto the MLR. We provide evidence that dopaminergic (DAergic) A13 neurons have connectivity to the cuneiform nucleus (CnF) and pedunculopontine tegmental nucleus (PPTg) of the MLR. No ascending connectivity to the dorsolateral striatum was observed. On the other hand, DAergic A13 projections to the medullary reticular formation (MRF) and the lumbar spinal cord were sparse. A small number of non-DAergic neurons within the medial ZI projected to the lumbar spinal cord. We then characterized the DA A13 cells and report that these cells differ from canonical DA neurons since they lack the Dopamine Transporter (DAT). The lack of DAT expression, and possibly the lack of a dopamine reuptake mechanism, points to a longer time of action compared to typical dopamine neurons. Collectively our data suggest a parallel descending DAergic pathway from the A13 neurons of the medial ZI to the MLR, which we expect is important for modulating movement.
Highlights
Dopaminergic (DAergic) locomotor control is associated with indirect innervations via ascending projections from the substantia nigra pars compacta (SNc) to the dorsal striatum (DSTR) that project onto the brainstem locomotor regions, and the motor cortex
DAergic A13 cells occupy a region in the medial aspect of the zona incerta (ZI), which in turn projects to a diverse range of targets that are important in motor control including the cerebellum, spinal cord, and red nucleus[16]
The animals included in the analysis had cuneiform nucleus (CnF) labeled as the core of the injection site (Supplementary Figure 1)
Summary
Dopaminergic (DAergic) locomotor control is associated with indirect innervations via ascending projections from the substantia nigra pars compacta (SNc) to the dorsal striatum (DSTR) that project onto the brainstem locomotor regions, and the motor cortex. DAergic A13 cells occupy a region in the medial aspect of the ZI, which in turn projects to a diverse range of targets that are important in motor control including the cerebellum, spinal cord, and red nucleus[16]. It remains to be tested if DAergic A13 cells project to the MLR. Our work demonstrates that the DAergic A13 nucleus provides a parallel descending dopaminergic connectivity to the MLR but not the ascending DAergic connectivity to DSTR These data expand our understanding of the descending DAergic connectome onto locomotor regions of the brainstem, providing evidence of direct DAergic pathways from the medial ZI onto the MLR. A portion of these data were published in an abstract form[30]
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