Intrinsic and Extrinsic Modulation of a Single Central Pattern Generating Circuit

Abstract

Intrinsic and extrinsic neuromodulation are both thought to be responsible for the flexibility of the neural circuits (central pattern generators) that control rhythmic behaviors. Because the two forms of modulation have been studied in different circuits, it has been difficult to compare them directly. We find that the central pattern generator for biting in Aplysia is modulated both extrinsically and intrinsically. Both forms of modulation increase the frequency of motor programs and shorten the duration of the protraction phase. Extrinsic modulation is mediated by the serotonergic metacerebral cell (MCC) neurons and is mimicked by application of serotonin. Intrinsic 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 mediated by CP-2 release. Although the effects of intrinsic and extrinsic modulation are similar, the neurons that mediate them are active predominantly at different times, suggesting a specialized role for each system. Metacerebral cell (MCC) activity predominates in the preparatory (appetitive) phase and thus precedes the activation of CBI-2 and biting motor programs. Once the CBI-2s are activated and the biting motor program is initiated, MCC activity declines precipitously. Hence extrinsic modulation prefacilitates biting, whereas intrinsic modulation occurs during biting. Since biting inhibits appetitive behavior, intrinsic modulation cannot be used to prefacilitate biting in the appetitive phase. Thus the sequential use of extrinsic and intrinsic modulation may provide a means for premodulation of biting without the concomitant disruption of appetitive behaviors.

Identification and Characterization of the Feeding Circuit-Activating Peptides, a Novel Neuropeptide Family ofAplysia

“…We used a system-oriented strategy that allowed us to identify and characterize a family of neuropeptides that induce rhythmic feeding motor output in Aplysia. This strategy took advantage of the fact that the CBCs fulfill a critical role in feeding behavior and that CBCs contain neuropeptides that act on the feeding circuitry (Sossin et al, 1987;Lloyd, 1989;Xin et al, 1999;Morgan et al, 2000Morgan et al, , 2002Jing and Weiss, 2001). MALDI analysis of the cut ends of the CBCs revealed a number of peaks, some of which are likely to represent novel peptides.…”

“…One of the preparations in which growing evidence indicates that peptidergic modulation plays an important role in initiation and regulation of behavior is Aplysia, in which neural circuits that mediate the consummatory phase of feeding behaviors are subject to extensive peptidergic modulation (Sossin et al, 1987;Xin et al, 1999;Morgan et al, 2000Morgan et al, , 2002Furukawa et al, 2001;Jing and Weiss, 2001). Previous work that has characterized some of the peptides in the feeding circuitry was performed on peptides that were originally identified from peripheral tissues or from other systems (Price and Greenberg, 1977;Morris et al, 1982;Cropper et al, 1987Cropper et al, , 1988.…”

Complementary Interactions between Command-Like Interneurons that Function to Activate and Specify Motor Programs

“…Here, we provide evidence suggesting that command neuron function may be more complex. Moreover, this study differs from previous research that has focused on command-like neurons that reliably trigger motor activity (Nolen and Hoy, 1984;Edwards et al, 1999;Eaton et al, 2001;Esch et al, 2002;Morgan et al, 2002;Flood et al, 2013). Not all command-like neurons fall into this category, so the functional contribution of this type of neuron is largely uncharacterized.…”

“…In other experiments, retraction was monitored by the sustained depolarization of the radula closing motor neuron B8 after protraction. In contrast to the phase invariance of the protraction-retraction sequence, the timing of radula opening-closing depends on the type of program Chiel, 1993a, 1993b;Church and Lloyd, 1994;Nargeot et al, 1997;Jing and Weiss, 2001;Morgan et al, 2002;Jing et al, 2010;Wu et al, 2010). Briefly, when B8 fires predominantly during retraction and thus (in the intact animal) helps bring food into the buccal cavity, the program is considered to be ingestive.…”

“…However, research on other multifunctional networks questions the generality of this scheme. Under different circumstances, one neuron drives different behaviors in cricket, leech, and Aplysia (Nolen and Hoy, 1984;Jing and Weiss, 2001;Esch et al, 2002;Morgan et al, 2002;Jing et al, 2004). Therefore, the latter studies suggest that command-like neurons, especially those that drive programs reliably, may function preferentially to trigger programs, rather than to specify their nature.…”