Loss of Sall3 eliminates presynaptic inhibition of sensory motor circuits and impairs adaptive motor behavior
- 1Stanford University
Abstract
Spinal presynaptic inhibitory interneurons are thought to regulate proprioceptive sensory feedback to shape motor output, however, their specific contribution to motor behavior has been difficult to assess, partially due to the lack of a specific genetic handle. Here, we identify Sall3 as the transcription factor required for the establishment and maintenance of GABApre axo-axonic synapses on proprioceptive Ia afferent terminals. Loss of Sall3 in mice selectively eliminates GABApre boutons on Ia afferent terminals, resulting in altered sensory-evoked motor responses and impaired skilled locomotor behaviors. Together, these findings establish Sall3 as a key regulator of GABApre circuit development and provide a genetic framework for understanding how presynaptic inhibition shapes sensorimotor integration.
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BibTeX
@misc{shadrach2026loss,
title = {{Loss of Sall3 eliminates presynaptic inhibition of sensory motor circuits and impairs adaptive motor behavior}},
author = {J. L. Shadrach and A. A. Mahrous and R. Palovics and Z. Saha and R. H. Roth and A. Panditrao and V. W. Y. Kan and M. A. Gradwell and V. E. Abraira and I. L. Llorente and J. B. Ding and T. Wyss-Coray and D. J. Bennett and C. Heckman and J. A. Kaltschmidt},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.25.746905},
url = {https://www.biorxiv.org/content/10.64898/2026.08.25.746905v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Loss of Sall3 eliminates presynaptic inhibition of sensory motor circuits and impairs adaptive motor behavior
AU - J. L. Shadrach
AU - A. A. Mahrous
AU - R. Palovics
AU - Z. Saha
AU - R. H. Roth
AU - A. Panditrao
AU - V. W. Y. Kan
AU - M. A. Gradwell
AU - V. E. Abraira
AU - I. L. Llorente
AU - J. B. Ding
AU - T. Wyss-Coray
AU - D. J. Bennett
AU - C. Heckman
AU - J. A. Kaltschmidt
PY - 2026
DA - 2026/08/25
PB - bioRxiv
DO - 10.64898/2026.08.25.746905
UR - https://www.biorxiv.org/content/10.64898/2026.08.25.746905v1
AB - Spinal presynaptic inhibitory interneurons are thought to regulate proprioceptive sensory feedback to shape motor output, however, their specific contribution to motor behavior has been difficult to assess, partially due to the lack of a specific genetic handle. Here, we identify Sall3 as the transcription factor required for the establishment and maintenance of GABApre axo-axonic synapses on proprioceptive Ia afferent terminals. Loss of Sall3 in mice selectively eliminates GABApre boutons on Ia afferent terminals, resulting in altered sensory-evoked motor responses and impaired skilled locomotor behaviors. Together, these findings establish Sall3 as a key regulator of GABApre circuit development and provide a genetic framework for understanding how presynaptic inhibition shapes sensorimotor integration.
ER -