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Author Notes:

E-mail: shawn.hochman@emory.edu

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subject:

Research Funding:

We gratefully acknowledge the following funding sources: NSF IOS-0745164 (Shawn Hochman); Paralyzed Veterans of America (Shawn Hochman); Craig H Neilsen Foundation (Shawn Hochman); NINDS F31 NS057911-02 (Elizabeth A. Gozal)

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • tyramine
  • tryptamine
  • beta-phenylethylamine
  • locomotion
  • TAAR
  • dopa decarboxylase
  • CENTRAL-NERVOUS-SYSTEM
  • CENTRAL PATTERN GENERATOR
  • VITRO NEONATAL-RAT
  • MEMBRANE MONOAMINE TRANSPORTER
  • BLOOD-BRAIN-BARRIER
  • IN-VITRO
  • BETA-PHENYLETHYLAMINE
  • ACID DECARBOXYLASE
  • OSCILLATORY PROPERTIES
  • SYNAPTIC-TRANSMISSION

Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord

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Journal Title:

Frontiers in Neural Circuits

Volume:

Volume 8

Publisher:

, Pages 134-134

Type of Work:

Article | Final Publisher PDF

Abstract:

The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na(+)-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na(+)-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic function.

Copyright information:

© 2014 Gozal, O'Neill, Sawchuk, Zhu, Halder, Chou and Hochman.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits distribution of derivative works, making multiple copies, distribution, public display, and publicly performance, provided the original work is properly cited. This license requires credit be given to copyright holder and/or author, copyright and license notices be kept intact.

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