Colocalized neuropeptides activate a central pattern generator by acting on different circuit targets.

In the presence of descending modulatory inputs, the stomatogastric ganglion (STG) of the lobster Homarus americanus generates a triphasic motor pattern, the pyloric rhythm. Red pigment-concentrating hormone (RPCH) and Cancer borealis tachykinin-related peptide (CabTRP) are colocalized in a pair of fibers that project into the neuropil of the STG. When the STG was isolated from anterior ganglia modulatory inputs, the lateral pyloric (LP) and pyloric (PY) neurons became silent, whereas the anterior burster (AB) and pyloric dilator (PD) neurons were rhythmically active at a low frequency. Exogenous application of 10(-6) m RPCH activated the LP neuron but not the PY neurons; 10(-6) m CabTRP activated the PY neurons but not the LP neuron. The actions of RPCH on the LP neuron and CabTRP on the PY neurons persisted when the rhythmic drive from the PD and AB neurons was removed, suggesting that the LP and PY neurons are direct targets for RPCH and CabTRP respectively. Coapplication of 10(-6) m RPCH and 10(-6) m CabTRP elicited triphasic motor patterns with phase relationships resembling those in a preparation with modulatory inputs intact. In summary, cotransmitters acting on different network targets act cooperatively to activate a complete central pattern-generating circuit.