An unrecognized family of neuromodulators control locomotion

Based on their low concentrations in mammalian brain, octopamine, β-phenylethylamine, tyramine, and tryptamine are classified as "trace" amines (TAs) and viewed as metabolic by-products. TAs are related to the classical monoamine transmitters and are synthesized from the same precursor aromatic amino acids. The recent discovery of a family of G protein-coupled receptors preferentially activated by TAs rekindled interest in TAs, but without a known circuitry, their function remains elusive and understudied. We now have anatomical evidence of an endogenous TA system in spinal cord, and show that the TAs recruit locomotor circuits and modulate ongoing locomotion. Our newest evidence suggest the TAs represent a parallel biochemical modulatory system that alters circuit function via a membrane transporter shuttling system that operates independent of synaptic actions. The long-term goal is to understand the physiological relevance of the TAs as an intrinsic modulatory system for subsequent therapeutic manipulation of spinal circuit function

Based on their low concentrations in mammalian brain, octopamine, beta -phenylethylamine (PEA), tyramine, and tryptamine are classified as " trace" amines (TAs) . TAs are related to the classical monoamine transmitters and are synthesized from the same precursor aromatic amino acids (AAs). Their CNS distribution is heterogeneous, and they have very high turnover rates, equivalent to that of DA and NA which “may be a more significant index of their importance than their endogenous concentrations” . Interest in TAs faded in the 80's viewing them as metabolic by-products. The seminal discovery in 2001 of a new family of G-protein coupled receptors preferentially activated by TAs rekindled interest in TAs. However, without a known circuitry, the function of TAs in CNS remains elusive and understudied.

We have found that the TAs (i) recruit locomotor circuits in the isolated spinal cord, (ii) can generate complex locomotor patterns, and (iii) modulate 5-HT's locomotor actions. The long-term goal is to understand the physiological relevance of the TAs as an intrinsic spinal modulatory system. TA-based actions may become valuable therapeutically to control spinal motor circuits following spinal cord injuries.

Trace amine-evoked locomotor-like activity in comparable to that produced by serotonin (5HT). Activity in a single ventral root on two time scales to show characteristic pattern of tyramine-evoked rhythmic motor activity.