Two Neuropeptides Colocalized in a Command-Like Neuron Use Distinct Mechanisms to Enhance Its Fast Synaptic Connection

Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029 Submitted 10 April 2003; accepted in final form 2 June 2003 In many neurons more than one peptide is colocalized with a classical neurotransmitter. The functional consequence of such an arrangement has been rarely investigated. Here, within the feeding circuit of Aplysia , we investigate at a single synapse the actions of two modulatory neuropeptides that are present in a cholinergic interneuron. In combination with previous work, our study shows that the command-like neuron for feeding, CBI-2, contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that high-frequency prestimulation or repeated stimulation of CBI-2 increases the size of CBI-2 to B61/62 excitatory postsynaptic potentials (EPSPs) and shortens the latency of firing of neuron B61/62 in response to CBI-2 stimulation. We find that both FCAP and CP2 mimic these two effects. The variance method of quantal analysis indicates that FCAP increases the calculated quantal size ( q ) and CP2 increases the calculated quantal content ( m ) of EPSPs. Since the PSP amplitude represents the product of q and m , the joint action of the two peptides is expected to be cooperative. This observation suggests a possible functional implication for multiple neuropeptides colocalized with a classical neurotransmitter in one neuron. Address for reprint requests: K. Weiss, Department of Physiology and Biophysics, Box 1218, Mount Sinai School of Medicine, New York, NY 10029 (E-mail: klaudiusz.weiss{at}mssm.edu ).