Intrinsic and extrinsic modulation of a single central pattern generating circuit

Intrinsic and extrinsic neuromodulation are both thought to be responsible for the flexibility of the neural circuits (central pattern generators) tha t control rhythmic behaviors. Because the two forms of modulation have been studied in different circuits, it has been difficult to compare them direc tly. We find that the central pattern generator for biting in Aplysia is mo dulated both extrinsically and intrinsically. Both forms of modulation incr ease the frequency of motor programs and shorten the duration of the protra ction phase. Extrinsic modulation is mediated by the serotonergic metacereb ral cell (MCC) neurons and is mimicked by application of serotonin. Intrins ic modulation is mediated by the cerebral peptide-2 (CP-2) containing CBI-2 interneurons and is mimicked by application of CP-2. Since the effects of CBI-2 and CP-2 occlude each other, the modulatory actions of CBI-2 may be m ediated by CP-2 release. Although the effects of intrinsic and extrinsic mo dulation are similar, the neurons that mediate them are active predominantl y at different times, suggesting a specialized role for each system. Metace rebral cell (MCC) activity predominates in the preparatory (appetitive) pha se and thus precedes the activation of CBI-2 and biting motor programs. Onc e the CBI-2s are activated and the biting motor program is initiated, MCC a ctivity declines precipitously. Hence extrinsic modulation prefacilitates b iting, whereas intrinsic modulation occurs during biting. Since biting inhi bits appetitive behavior, intrinsic modulation cannot be used to prefacilit ate biting in the appetitive phase. Thus the sequential use of extrinsic an d intrinsic modulation may provide a means for premodulation of biting with out the concomitant disruption of appetitive behaviors.