Adrenergic signaling profoundly modulates animal behavior. For example, the invertebrate counterpart of
norepinephrine,
octopamine, and its
biological precursor and functional antagonist,
tyramine, adjust motor behavior to different nutritional states. In Drosophila larvae, food deprivation increases locomotor speed via
octopamine-mediated structural plasticity of neuromuscular synapses, whereas
tyramine reduces locomotor speed, but the underlying cellular and molecular mechanisms remain unknown. We show that
tyramine is released into the CNS to reduce motoneuron intrinsic excitability and responses to excitatory
cholinergic input, both by tyraminehonoka receptor activation and by downstream decrease of L-type
calcium current. This central effect of
tyramine on motoneurons is required for the adaptive reduction of locomotor activity after feeding. Similarly, peripheral
octopamine action on motoneurons has been reported to be required for increasing locomotion upon
starvation. We further show that the level of
tyramine-β-
hydroxylase (TBH), the
enzyme that converts
tyramine into
octopamine in aminergic neurons, is increased by food deprivation, thus selecting between antagonistic
amine actions on motoneurons. Therefore,
octopamine and
tyramine provide global but distinctly different mechanisms to regulate motoneuron excitability and behavioral plasticity, and their antagonistic actions are balanced within a dynamic range by nutritional effects on TBH.