Background & Aims
Adult mice exhibit a fast, precise and specific withdrawal reflex in response to noxious stimuli (1). However, newborn pups will equally withdraw from innocuous touch, due to highly sensitive immature somatosensory circuits. Reflex modulation relies, in part, on a feedback loop between the primary somatosensory cortex (SI) and the spinal cord, which facilitates brush-sensitivity in the adult mouse(2). Interestingly, the maturation of the CST has been suggested to occur over the same time course as that of somatosensory behaviours. However, it is unknown when the axonal projections of the somatosensory CST reach anatomical maturity to effectively engage local spinal circuitry and consequently influence somatosensory behaviour. Here, we aimed to anatomically trace the postnatal maturation of the mouse S1-CST originating from the cortical representation of the hind limb (S1hl) into the lumbar spinal cord.
Methods
To examine the anatomical maturation of the somatosensory corticospinal tract, we labelled S1hl-CST projection neurons by injecting mice at different postnatal ages (P0-P56) with either (1) a retrograde tracer, Fluoro-Gold (FG), into the dorsal lumbar cord or (2) an anterograde AAV9 viral vector in the S1hl. We then used confocal imaging to track the timecourse of S1hl-CST innervation into the lumbar spinal cord.
Results
S1hl CST projections did not reach lumbar spinal segments until postnatal day P9. Within the next few days of arrival, at P12, number of S1hl CST projections reaches mature levels. S1hl CST branching within the dorsal horn at this age was, however, found to terminate widely throughout the dorsal grey matter, beyond the adult laminar termination patterns. Terminal branch pattern was then found to refine until P17, where they matched projection patterns observed in the adult.
Conclusions
Our results provide a detailed timeline of the anatomical development of corticospinal projections from the S1hl in the mouse and suggest that the maturation of S1-CST projections is not complete before P17. Having established that the development of the S1hl-CST occurs between P7 and P17, this opens the possibility to investigate the role of this late developing circuit in the postnatal maturation of low threshold somatosensory behaviours.
References
1. Waldenström, A., Thelin, J., Thimansson, E., Levinsson, A., & Schouenborg, J. (2003).
Developmental learning in a pain-related system: evidence for a cross-modality
mechanism. Journal of Neuroscience, 23(20), 7719–7725.
2. Liu, Y., Latremoliere, A., Li, X., Zhang, Z., Chen, M., Wang, X., Fang, C., Zhu, J., Alexandre, C.,
Gao, Z., Chen, B., Ding, X., Zhou, J.-Y., Zhang, Y., Chen, C., Wang, K. H., Woolf, C. J., & He,
Z. (2018). Touch and tactile neuropathic pain sensitivity are set by corticospinal
projections. Nature, 561(7724), 547–550. https://doi.org/10.1038/s41586-018-0515-
Presenting Author
Antonia Maria Constantinescu
Poster Authors
Antonia Constantinescu
MSc
University College London
Lead Author
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)