Abstract:

The trace amines (TAs) comprise a class of neuroactive monoamines that are synthesized from the same precursor amino acids and essential synthesis enzyme as the classical monoamine modulatory transmitters [Figure 1]. This perspective report re-appraises their role in relation to our recent findings on their unique motor facilitatory actions. (1) I first provide an overview of the TAs. Their detectability in trace amounts due to lack of storage led not only to their name but also to an expression lability that made it difficult to ascribe a role in CNS function but easy to dismiss as metabolic byproducts. The 2001 discovery of G-protein coupled trace amine-associated receptors (TAARs) preferentially activated by TAs established a mechanisms by which TAs can produce effects of their own, and inspired new investigations that placed the TAAR1 receptor as a component of brain monoaminergic signaling. Still, without identification of discrete trace aminergic neuronal circuits, their role in CNS modulation remains uncertain.(2) I then describe our results in the neonatal rat spinal cord showing that the TAs can facilitate expression of spinal locomotor patterns independent of, but with comparable ability to, descending monoamines. Additional results support the TAs as a distinct class intrinsic monoaminergic neuromodulators acting intracellularly, putatively on TAARs. (3)The functional relevance of the TAs to behavior is then explored as an adaptive intracellular metabolic effector, and in tonically setting spinal circuit excitability. (4) Finally, emphasis on the need for additional experiments including in the adult segues into possible neurotherapeutic approaches that modulate spinal cord function with facilitated expression of locomotor circuits after spinal cord injury as an example.