Peptide cotransmitter release from motorneuron B16 in Aplysia californica:Costorage, corelease, and functional implications

Many neurons contain multiple peptide cotransmitters in addition to their c lassical transmitters. We are using the accessory radula closer neuromuscul ar system of Aplysia, which participates in feeding in these animals, to de fine the possible consequences of multiple modulators converging on single targets. How these modulators are released onto their targets is of critica l importance in understanding the outcomes of their modulatory actions and their physiological role. Here we provide direct evidence that the partiall y antagonistic families of modulatory peptides, the myomodulins and buccali ns, synthesized by motorneuron B16 are costored and coreleased in fixed rat ios. We show that this release is calcium-dependent and independent of musc le contraction. Furthermore, we show that peptide release is initiated at t he low end of the physiological range of motorneuron firing frequency and t hat it increases with increasing motorneuron firing frequency. The coordina tion of peptide release with the normal operating range of a neuron may be a general phenomenon and suggests that the release of peptide cotransmitter s may exhibit similar types of regulation and plasticity as have been obser ved for classical transmitters. Stimulation paradigms that increase muscle contraction amplitude or frequency also increase peptide release from motor neuron B16. The net effect of the modulatory peptide cotransmitters releas ed from motorneuron B16 would be to increase relaxation rate and therefore allow more frequent and/or larger contractions to occur without increased r esistance to antagonist muscles. The end result of this modulation could be to maximize the efficiency of feeding.