Deep brain stimulation of the mesencephalic locomotor centre induces stimulation-dependent behavioural states beyond locomotion
- 1University Hospital Wurzburg
Abstract
Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been explored to treat gait disturbances. However, clinical outcomes of MLR-DBS have been disappointing overall, with only modest benefits in some individuals and unwanted effects, including anxiety, reported in others. Preclinical studies in several species, by contrast, show that MLR-DBS can improve locomotor and gait deficits, although defensive behaviours in response to stimulation have also been reported in some species. To investigate this discrepancy, we examined frequency- and amplitude-dependent effects of MLR-DBS in healthy rats, combining semi-supervised and unsupervised behavioural analyses. High-frequency, high-amplitude DBS (80-130 Hz), but not low-frequency stimulation (20-60 Hz), elicited hyperlocomotion intermixed with acute defensive-like behaviours. Low-frequency stimulation instead promoted phases of immobility. Consistently, only high-frequency DBS induced region-specific c-Fos expression in the MLR. Complex behaviours, including hyperlocomotion, rearing, tail rattling, and periods of immobility, were most pronounced in animals with the DBS electrode tip localized to the cuneiform nucleus (CnF) of the MLR. Using AAV tracer constructs for bright labelling of CaMKII-positive neurons and their axons, we identified prominent ascending projections from the CnF to the thalamus, substantia nigra pars compacta, zona incerta, hypothalamus, subthalamic nucleus, and central amygdala (CeA). Retrograde tracing confirmed the CnF-to-CeA projection independently. These findings show that the MLR is anatomically connected to higher-order centres linking motor and defensive networks, with DBS frequency and amplitude critically shaping behavioural outcomes that extend beyond locomotion.
Related
- Serotonergic modulation of sacral dorsal root stimulation-induced locomotor output in newborn rat
- Daily locomotor rhythms and ecdysial stage-dependent behaviors in the tardigrade Hypsibius exemplaris
- Orsay virus infection is associated with reduced locomotion and alters cue-dependent food choice in Caenorhabditis elegans
- A step beyond: age and sex-dependent changes in multidimensional locomotor and gait patterns of voluntary motion of C57BL/6 mice
- Experience-dependent shifts in behavioural decision-making following repeated captures in a wild mammal
BibTeX
@misc{wilhelm2026deep,
title = {{Deep brain stimulation of the mesencephalic locomotor centre induces stimulation-dependent behavioural states beyond locomotion}},
author = {M. Wilhelm and J. Hartig and T. C. Faupel and D. Sun and S. M. Moritz and J. Signoret-Genest and F. Hakimi and A. Sodmann and F. Schlott and S. Knorr and P. Tovote and C. W. Ip and F. Fluri and M. K. Schuhmann and J. Volkmann and R. Blum},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.752305},
url = {https://www.biorxiv.org/content/10.64898/2026.09.18.752305v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Deep brain stimulation of the mesencephalic locomotor centre induces stimulation-dependent behavioural states beyond locomotion
AU - M. Wilhelm
AU - J. Hartig
AU - T. C. Faupel
AU - D. Sun
AU - S. M. Moritz
AU - J. Signoret-Genest
AU - F. Hakimi
AU - A. Sodmann
AU - F. Schlott
AU - S. Knorr
AU - P. Tovote
AU - C. W. Ip
AU - F. Fluri
AU - M. K. Schuhmann
AU - J. Volkmann
AU - R. Blum
PY - 2026
DA - 2026/09/18
PB - bioRxiv
DO - 10.64898/2026.09.18.752305
UR - https://www.biorxiv.org/content/10.64898/2026.09.18.752305v1
AB - Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been explored to treat gait disturbances. However, clinical outcomes of MLR-DBS have been disappointing overall, with only modest benefits in some individuals and unwanted effects, including anxiety, reported in others. Preclinical studies in several species, by contrast, show that MLR-DBS can improve locomotor and gait deficits, although defensive behaviours in response to stimulation have also been reported in some species. To investigate this discrepancy, we examined frequency- and amplitude-dependent effects of MLR-DBS in healthy rats, combining semi-supervised and unsupervised behavioural analyses. High-frequency, high-amplitude DBS (80-130 Hz), but not low-frequency stimulation (20-60 Hz), elicited hyperlocomotion intermixed with acute defensive-like behaviours. Low-frequency stimulation instead promoted phases of immobility. Consistently, only high-frequency DBS induced region-specific c-Fos expression in the MLR. Complex behaviours, including hyperlocomotion, rearing, tail rattling, and periods of immobility, were most pronounced in animals with the DBS electrode tip localized to the cuneiform nucleus (CnF) of the MLR. Using AAV tracer constructs for bright labelling of CaMKII-positive neurons and their axons, we identified prominent ascending projections from the CnF to the thalamus, substantia nigra pars compacta, zona incerta, hypothalamus, subthalamic nucleus, and central amygdala (CeA). Retrograde tracing confirmed the CnF-to-CeA projection independently. These findings show that the MLR is anatomically connected to higher-order centres linking motor and defensive networks, with DBS frequency and amplitude critically shaping behavioural outcomes that extend beyond locomotion.
ER -