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Postnatal maturation of serotonergic modulation of spinal RORβ interneurons in the medial deep dorsal horn
Preprint   Open access

Postnatal maturation of serotonergic modulation of spinal RORβ interneurons in the medial deep dorsal horn

Christopher W West, D Leonardo Garcia-Ramirez and Kimberly J Dougherty
bioRxiv
17 Nov 2024
DOI: https://doi.org/10.1101/2024.11.15.623295
PMID: 39605347
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601448View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Proprioceptive input is essential for coordinated locomotion and this input must be properly gated to ensure smooth and effective movement. Presynaptic inhibition mediated by GABAergic interneurons provides regulation of sensory afferent feedback. Serotonin not only promotes locomotion, but also modulates feedback from sensory afferents, both directly and indirectly, potentially by acting on the GABAergic interneurons that mediate presynaptic inhibition. Developmental disruptions in presynaptic inhibition can produce deficits in sensorimotor processing. Importantly, both presynaptic inhibition of proprioceptive afferents and serotonergic innervation of the spinal cord become mature and functional after the first postnatal week. However, little is known about the serotonergic receptors involved in the modulation of interneurons mediating presynaptic inhibition and when developmentally their actions mature. Here, we used whole-cell patch clamp recordings in lumbar spinal slices from neonatal and juvenile mice to assess the intrinsic properties and serotonergic modulation of deep dorsal horn GABAergic RORβ interneurons previously shown to mediate presynaptic inhibition of proprioceptive afferents. RORβ interneurons from juvenile cords displayed more mature membrane properties. Further, serotonin increased the excitability of RORβ interneurons via actions at 5-HT , 5-HT , and 5-HT receptors in juvenile but not early neonatal spinal cords. Our findings indicate that deep dorsal horn RORβ interneurons undergo postnatal maturation in both their intrinsic excitability and ability to respond to serotonin, concurrent with the maturation of serotonergic innervation of the dorsal horn. This information can prompt future targeted studies testing relationships between impairments of serotonergic development, proprioceptive processing disorders, and presynaptic inhibition mediated by RORβ interneurons.

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