title: Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord.
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.
authors.affiliation: Physiology Department, Emory University Atlanta, GA, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gozal
authors.affiliation: Physiology Department, Emory University Atlanta, GA, USA.
authors.forename: Brannan E
authors.initials: BE
authors.lastname: O'Neill
authors.affiliation: Physiology Department, Emory University Atlanta, GA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sawchuk
authors.affiliation: Physiology Department, Emory University Atlanta, GA, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Physiology Department, Emory University Atlanta, GA, USA.
authors.forename: Mallika
authors.initials: M
authors.lastname: Halder
authors.affiliation: Physiology Department, Emory University Atlanta, GA, USA.
authors.forename: Ching-Chieh
authors.initials: CC
authors.lastname: Chou
authors.affiliation: Physiology Department, Emory University Atlanta, GA, USA.
authors.forename: Shawn
authors.initials: S
authors.lastname: Hochman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism; D063226:Central Pattern Generators / Q000187:drug effects / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D014363:Tryptamines / Q000096:biosynthesis / Q000378:metabolism*; D014439:Tyramine / Q000096:biosynthesis / Q000378:metabolism*; D000095383:Trace Amine-Associated Receptors
chemical_list: D001142:Aromatic-L-Amino-Acid Decarboxylases; D015306:Biogenic Monoamines; D016202:N-Methylaspartate; D010627:Phenethylamines; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin; D014363:Tryptamines; D014439:Tyramine; D000095383:Trace Amine-Associated Receptors; C582779:TAAR4 protein, rat; C029261:phenethylamine; C030820:tryptamine
keywords: TAAR; dopa decarboxylase; locomotion; tryptamine; tyramine; β-phenylethylamine