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Activation of α-adrenoceptors depresses synaptic transmission of myelinated afferents and inhibits pathways mediating primary afferent depolarization (PAD) in the in vitro mouse spinal cord

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Abstract

Somatosensory afferent transmission strength is controlled by several presynaptic mechanisms that reduce transmitter release at the spinal cord level. We focused this investigation on the role of α-adrenoceptors in modulating sensory transmission in low-threshold myelinated afferents and in pathways mediating primary afferent depolarization (PAD) of neonatal mouse spinal cord. We hypothesized that the activation of α-adrenoceptors depresses low threshold-evoked synaptic transmission and inhibits pathways mediating PAD. Extracellular field potentials (EFPs) recorded in the deep dorsal horn assessed adrenergic modulation of population monosynaptic transmission, while dorsal root potentials (DRPs) recorded at root entry zone assessed adrenergic modulation of PAD. We found that noradrenaline (NA) and the α1-adrenoceptor agonists phenylephrine and cirazoline depressed synaptic transmission (by 15, 14 and 22%, respectively). DRPs were also depressed by NA, phenylephrine and cirazoline (by 62, 30, and 64%, respectively), and by the α2-adrenoceptor agonist clonidine, although to a lower extent (20%). We conclude that NA depresses monosynaptic transmission of myelinated afferents onto deep dorsal horn neurons via α1-adrenoceptors and inhibits interneuronal pathways mediating PAD through the activation of α1- and α2-adrenoceptors. The functional significance of these modulatory actions in shaping cutaneous and muscle sensory information during motor behaviors requires further study.

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Funding

National Institute of Neurological Disorders and Stroke (NS-065949). Consejo Nacional de Ciencia y Tecnología (Conacyt-59873).

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All authors contributed to the conception and design of the study. Material preparation, data collection, and analysis were performed by Elvia Mena-Avila and Jonathan J. Milla-Cruz. The first draft of the manuscript was written by Elvia Mena-Avila and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jorge N. Quevedo.

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The authors declare that they have no conflict of interest.

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Communicated by Winston D. Byblow.

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Mena-Avila, E., Milla-Cruz, J.J., Calvo, J.R. et al. Activation of α-adrenoceptors depresses synaptic transmission of myelinated afferents and inhibits pathways mediating primary afferent depolarization (PAD) in the in vitro mouse spinal cord. Exp Brain Res 238, 1293–1303 (2020). https://doi.org/10.1007/s00221-020-05805-y

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  • DOI: https://doi.org/10.1007/s00221-020-05805-y

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