Removal of endogenous neuromodulators in a small motor network enhances responsiveness to neuromodulation

We studied the changes in sensitivity to a peptide modulator, crustacean cardioactive peptide (CCAP), as a response to loss of endogenous modulation in the stomatogastric ganglion (STG) of the crab, Cancer borealis. Our data demonstrate that removal of endogenous modulation for 24 hours increases the response of the LP neuron of the STG to exogenously applied CCAP. Increased responsiveness is accompanied by increases in CCAP receptor (CCAPr) mRNA levels in LP neurons, requires de novo protein synthesis, and can be prevented by co-incubation for the 24 hour period with exogenous CCAP. These results suggest that there is a direct feedback from loss of CCAP signaling to the production of CCAPr that increases subsequent response to the ligand. However, we also demonstrate that the modulator-evoked membrane current (IMI) activated by CCAP is greater in magnitude following combined loss of endogenous modulation and activity, compared with removal of just hormonal modulation. These results suggest that both receptor expression and an increase in the target conductance of the CCAP G-protein coupled receptor are involved in the increased response to exogenous hormone exposure following experimental loss of modulation in the STG.

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