Descending Dopaminergic Inputs to Reticulospinal Neurons Promote Locomotor Movements
JOURNAL OF NEUROSCIENCE
Authors: Ryczko, Dimitri; Gratsch, Swantje; Alpert, Michael H.; Cone, Jackson J.; Kasemir, Jacquelin; Ruthe, Angelina; Beausejour, Philippe-Antoine; Auclair, Francois; Roitman, Mitchell F.; Alford, Simon; Dubuc, Rejean
Abstract
Meso-diencephalic dopaminergic neurons are known to modulate locomotor behaviors through their ascending projections to the basal ganglia, which in turn project to the mesencephalic locomotor region, known to control locomotion in vertebrates. In addition to their ascending projections, dopaminergic neurons were found to increase locomotor movements through direct descending projections to the mesencephalic locomotor region and spinal cord. Intriguingly, fibers expressing tyrosine hydroxylase (TH), the ratelimiting enzyme of dopamine synthesis, were also observed around reticulospinal neurons of lampreys. We now examined the origin and the role of this innervation. Using immunofluorescence and tracing experiments, we found that fibers positive for dopamine innervate reticulospinal neurons in the four reticular nudei of lampreys. We identified the dopaminergic source using tracer injections in reticular nuclei, which retrogradely labeled dopaminergic neurons in a caudal diencephalic nucleus (posterior tuberculum WTI). Using voltammetry in brain preparations isolated in vitro, we found that PT stimulation evoked dopamine release in all four reticular nuclei, but not in the spinal cord. In semi-intact preparations where the brain is accessible and the body moves, PT stimulation evoked swimming, and injection of a D-1 receptor antagonist within the middle rhombencephalic reticular nucleus was sufficient to decrease reticulospinal activity and PT-evoked swimming. Our study reveals that dopaminergic neurons have access to command neurons that integrate sensory and descending inputs to activate spinal locomotor neurons. As such, our findings strengthen the idea that dopamine can modulate locomotor behavior both via ascending projections to the basal ganglia and through descending projections to brainstem motor circuits.
Delayed Treatment With Low-intensity Extracorporeal Shock Wave Therapy in an Irreversible Rat Model of Stress Urinary Incontinence
UROLOGY
Authors: Zhang, Xiaoyu; Ruan, Yajun; Wu, Alex K.; Zaid, Uwais; Villalta, Jaqueline D.; Wang, Guifang; Banie, Lia; Reed-Maldonado, Amanda B.; Lin, Guiting; Lue, Tom F.
Abstract
OBJECTIVE To determine the outcomes and mechanisms of delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) in a rat model of irreversible stress urinary incontinence (SUI). MATERIALS AND METHODS Twenty-four female Sprague-Dawley rats were randomly assigned into 3 groups: sham control, vaginal balloon dilation + beta-aminopropionitrile (BAPN; SUI group), and vaginal balloon dilation + BAPN + treatment with Li-ESWT (SUI-Li-ESWT group). An irreversible SUI model was developed by inhibiting the urethral structural recovery with BAPN daily for 5 weeks. Thereafter, in the SUI-Li-ESWT group, Li-ESWT was administered twice per week for 2 weeks. After a 1-week washout, all 24 rats were evaluated with functional and histologic studies at 17 weeks of age. Endogenous progenitor cells were detected via the EdU-labeling method. RESULTS Functional analysis with leak point pressure testing showed that the SUI-Li-ESWT group had significantly higher leak point pressures compared with untreated rats. Increased urethral and vaginal smooth and striated muscle content and increased thickness of the vaginal wall were noted in the SUI-Li-ESWT group. The SUI group had significantly decreased neuronal nitric oxide/tyrosine hydroxylase positive nerves ratio in the smooth muscle layers of the urethra, while the SUI-Li-ESWT group had neuronal nitric oxide/tyrosine hydroxylase+ nerves ratio similar to that of the control group. The continuality of urothelial cell lining was also improved in the SUI-Li-ESWT group. In addition, there were significantly increased EdU-positive cells in the SUI-Li-ESWT group. CONCLUSION Li-ESWT appears to increase smooth muscle content in the urethra and the vagina, increase the thickness of urethral wall, improve striated muscle content and neuromuscular junctions, restore the integrity of the urothelium, and increase the number of EdU-retaining progenitor cells in the urethral wall. (C) 2020 Elsevier Inc.