Dopamine release in the medullary reticular formation is related to locomotor velocity
Abstract
Dopamine is classically recognized for modulating locomotion through basal ganglia circuits. However, it also modulates motor circuits in the brainstem and spinal cord. The medullary reticular formation (MRF) integrates supraspinal motor commands and relays them to the spinal cord, yet the role of dopamine in this region is poorly understood. Using the genetically encoded dopamine sensor dLight1.4, we observed that dopamine release in the MRF decreased during the initiation of locomotion and showed an inverse correlation with locomotor velocity. Dopamine release was also modulated during directional head turns. RNA in situ hybridization revealed D ₂ R mRNA expression is present in about one-third of glutamatergic reticulospinal neurons (RSNs), whereas D ₄ R mRNA expression is nearly absent. Retrograde viral tracing identified the A11 region, encompassing dopaminergic TH ⁺ cells, as the primary source of dopaminergic input to the MRF, with minimal contributions from other dopaminergic nuclei. Anterograde tracing demonstrated that A11 neurons project ipsilaterally throughout the rostrocaudal MRF and form putative synaptic contacts with neuronal populations that project to the spinal cord. These findings reveal discrete dopaminergic projections from the A11 region to the MRF and lead to the hypothesis that the A11–MRF dopaminergic pathway acts as a gain-control mechanism setting the excitability of D ₂ receptor-expressing reticulospinal neurons, thereby providing state-dependent control of locomotor speed.
Significance Statement The medullary reticular formation (MRF) is a critical hub for controlling diverse motor behaviors; however, the source and organization of its dopaminergic inputs remain unclear. Here we identify A11 dopamine neurons as the principal dopaminergic projection to the MRF. Dopamine signaling in the MRF correlates inversely with locomotor velocity and is modulated during ipsilateral head turns. Furthermore, the expression of D ₂ Rs on glutamatergic reticulospinal neurons identifies these cells as primary targets for dopaminergic modulation.
Related
- Perceptual sensitivity supports online control, while perceptual errors drive motor memory formation during locomotor adaptation
- Glutamatergic Neurons in caudal Pontine Reticular Nucleus (PRNc) Mediate Backward Locomotion in mice
- Single-cell dataset of juvenile mouse neurons from the thalamic reticular nucleus: whole-cell patch-clamp electrophysiology
- Neurodegeneration-inducing macromolecules exit the brain via nanovascular conduits formed by reticular fibroblasts
- Medullary epithelium-free areas in the rat thymus are specialized niches enriched for mature thymocytes and distinct stromal subsets
BibTeX
@article{grams2026dopamine,
title = {{Dopamine release in the medullary reticular formation is related to locomotor velocity}},
author = {Joseph R. Grams and Cecilia A. Badenhorst and Michelle A. Tran and Jonathan J. Milla Cruz and David A. Elliott and Theodore L. Nelson and Elizabeth M.S. Thurston and Rebecca K. John and Sandeep Sharma and Catalina Ortega and Patrick J. Whelan},
journal = {eneuro},
year = {2026},
month = oct,
doi = {10.1523/eneuro.0292-26.2026},
url = {https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0292-26.2026},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - JOUR
TI - Dopamine release in the medullary reticular formation is related to locomotor velocity
AU - Joseph R. Grams
AU - Cecilia A. Badenhorst
AU - Michelle A. Tran
AU - Jonathan J. Milla Cruz
AU - David A. Elliott
AU - Theodore L. Nelson
AU - Elizabeth M.S. Thurston
AU - Rebecca K. John
AU - Sandeep Sharma
AU - Catalina Ortega
AU - Patrick J. Whelan
PY - 2026
DA - 2026/10/29
JO - eneuro
DO - 10.1523/eneuro.0292-26.2026
UR - https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0292-26.2026
AB - Dopamine is classically recognized for modulating locomotion through basal ganglia circuits. However, it also modulates motor circuits in the brainstem and spinal cord. The medullary reticular formation (MRF) integrates supraspinal motor commands and relays them to the spinal cord, yet the role of dopamine in this region is poorly understood. Using the genetically encoded dopamine sensor dLight1.4, we observed that dopamine release in the MRF decreased during the initiation of locomotion and showed an inverse correlation with locomotor velocity. Dopamine release was also modulated during directional head turns. RNA in situ hybridization revealed D ₂ R mRNA expression is present in about one-third of glutamatergic reticulospinal neurons (RSNs), whereas D ₄ R mRNA expression is nearly absent. Retrograde viral tracing identified the A11 region, encompassing dopaminergic TH ⁺ cells, as the primary source of dopaminergic input to the MRF, with minimal contributions from other dopaminergic nuclei. Anterograde tracing demonstrated that A11 neurons project ipsilaterally throughout the rostrocaudal MRF and form putative synaptic contacts with neuronal populations that project to the spinal cord. These findings reveal discrete dopaminergic projections from the A11 region to the MRF and lead to the hypothesis that the A11–MRF dopaminergic pathway acts as a gain-control mechanism setting the excitability of D ₂ receptor-expressing reticulospinal neurons, thereby providing state-dependent control of locomotor speed. Significance Statement The medullary reticular formation (MRF) is a critical hub for controlling diverse motor behaviors; however, the source and organization of its dopaminergic inputs remain unclear. Here we identify A11 dopamine neurons as the principal dopaminergic projection to the MRF. Dopamine signaling in the MRF correlates inversely with locomotor velocity and is modulated during ipsilateral head turns. Furthermore, the expression of D ₂ Rs on glutamatergic reticulospinal neurons identifies these cells as primary targets for dopaminergic modulation.
SN - 2373-2822
ER -