Composite Modulatory Feedforward Loop Contributes to the Establishment of a Network State

Abstract

Wu JS, Vilim FS, Hatcher NG, Due MR, Sweedler JV, Weiss KR, Jing J. Composite modulatory feedforward loop contributes to the establishment of a network state. J Neurophysiol 103: 2174-2184, 2010. First published February 24, 2010 doi:10.1152/jn.01054.2009 are one of many network motifs identified in a variety of complex networks, but their functional role in neural networks is not well understood. We provide evidence that combinatorial actions of multiple modulators may be organized as FFLs to promote a specific network state in the Aplysia feeding motor network. The Aplysia feeding central pattern generator (CPG) receives two distinct inputs-a higher-order interneuron cerebral-buccal interneuron-2 (CBI-2) and the esophageal nerve (EN)-that promote ingestive and egestive motor programs, respectively. EN stimulation elicits a persistent egestive network state, which enables the network to temporarily express egestive programs following a switch of input from the EN to CBI-2. Previous work showed that a modulatory CPG element, B65, is specifically activated by the EN and participates in establishing the egestive state by enhancing activity of egestion-promoting B20 interneurons while suppressing activity and synaptic outputs of ingestion-promoting B40 interneurons. Here a peptidergic contribution is mediated by small cardioactive peptide (SCP). Immunostaining and mass spectrometry show that SCP is present in the EN and is released on EN stimulation. Importantly, SCP directly enhances activity and synaptic outputs of B20 and suppresses activity and synaptic outputs of B40. Moreover, SCP promotes B65 activity. Thus the direct and indirect (through B65) pathways to B20 and B40 from SCPergic neurons constitute two FFLs with one functioning to promote egestive output and the other to suppress ingestive output. This composite FFL consisting of the two combined FFLs appears to be an effective means to co-regulate activity of two competing elements that do not inhibit each other, thereby contributing to establish specific network states.

Characterization of GdFFD, a d-Amino Acid-containing Neuropeptide That Functions as an Extrinsic Modulator of the Aplysia Feeding Circuit

“…Although we do not yet know under what circumstances GdFFD-positive neurons would be activated, it is attractive to speculate that GdFFD may function to interrupt ingestion when locomotion is active because the pedal ganglion is involved in the control of locomotion (83). In this sense, in contrast to the actions of intrinsic modulators apNPY and SCP, the extrinsic modulator GdFFD might provide a new context in which a modulator may bias the feeding programs toward egestion in the Aplysia feeding system (41,47). To the best of our knowledge, GdFFD represents the first example of a DAACP acting on a defined neural circuit that ultimately influences behavior.…”

“…The lack of YdAEFLa and the presence of GdFFD may have implications for the evolution of peptide functions and demonstrates that sequence similarity is not enough to conclude that the PTM present in the peptide from one species is also present in another. We then examined the bioactivity of GFFD/GdFFD in the well described Aplysia feeding circuit (41)(42)(43)(44)(45)(46)(47)(48). We found that only GdFFD is bioactive and, moreover, that it functions as an extrinsic modulator of the feeding circuit.…”

Effects of aversive stimuli beyond defensive neural circuits: Reduced excitability in an identified neuron critical for feeding in Aplysia

“…A simple interpretation of this experimental outcome is that 5-HT does not mediate the suppression of feeding produced by LTS training, thus suggesting that an additional modulator(s), triggered by sensitizing stimuli, modifies the activity of the feeding neural circuit. In this case, modulators, such as the small cardioactive peptide (SCP) and nitric oxide (NO), might be putative candidates to mediate the effects of LTS training because they modulate the feeding neural circuit in Aplysia (Wu et al 2010;Susswein and Chiel 2012). However, it must be noted that the modulatory role of 5-HT in the feeding circuit is rather complex and not fully understood.…”

Coordination of Distinct Motor Structures through Remote Axonal Coupling of Projection Interneurons

“…In other experiments, retraction was monitored by the sustained depolarization of the radula closing motoneuron B8 following protraction. In contrast to the phase-invariance of the protraction-retraction sequence, the timing of radula opening-closing depends on the type of program (Morton and Chiel, 1993a,b; 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 the food into the buccal cavity, the program is considered to be ingestive.…”