Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation

Abstract

Feeding behaviour is modulated by both environmental cues and internal physiological states. Appetite is commonly boosted by the pleasant smell (or appearance) of food and destroyed by a bad taste. In reality, animals sense multiple environmental cues at the same time and it is not clear how these sensory inputs are integrated and a decision is made to regulate feeding behaviour accordingly. Here we show that feeding behaviour in Caenorhabditis elegans can be either facilitated by attractive odours or suppressed by repellents. By identifying mutants that are defective for sensory-mediated feeding regulation, we dissected a central flip-flop circuit that integrates two contradictory sensory inputs and generates bistable hormone output to regulate feeding behaviour. As feeding regulation is fundamental to animal survival, we speculate that the basic organizational logic identified here in C. elegans is likely convergent throughout different phyla.

Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception and avoidance in Caenorhabditis elegans

“…ASI functions as a modulator to suppress hyper-nociception and fine-tune worm avoidance behaviour. This circuit is similar to the central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation 52 . However, there are differences between the two circuits: (1) the central feeding regulatory circuit integrates two different sets of sensory information from the olfactory attractive cues and the gustatory or the olfactory repellents, whereas the peripheral circuit receives the same sensory information from gustatory nociceptive stimuli; (2) the kinetics of the two circuits are different, as the peripheral circuit is biased and progress dependent, whereas the central circuit is bistable and fast switchable, although the nociceptive sensory information has more effects than that of attraction; and (3) their functions are different, in that the central circuit functions to make a rapid decision, whereas the peripheral circuit fine-tunes nociceptive sensation and suppress hyper-responding behaviour.…”

Multiple Sensory Inputs Are Extensively Integrated to Modulate Nociception in C. elegans

“…For example, the prolonged ASH and AIB signaling off food could trigger the release of additional modulatory neuropeptides or enhance signaling to the RIMs, the major synaptic partner of the AIBs that are involved in the initiation of an turn (Donnelly et al, 2013). Interestingly, a related flip/flop circuit modulating pharyngeal pumping has also been identified recently in C. elegans, in which pharyngeal pumping stimulated by the AWA sensory neurons remains constant in the face of an increasing concentration of repellant perceived by the ASHs until a critical repellant threshold is achieved, at which point pumping decreases rapidly (Li et al, 2012). Presumably, this system also facilitates maximal feeding in an unfavorable environment until the cost of the feeding becomes too great, at which point the animals cease feeding and presumably exit, suggesting that additional locomotory phenotypes also may couple to this flip/flop circuit associated with feeding, some of which are suggested by the present study.…”

Neural Circuits: From Structure to Function and Back

“…The results described by Bhatla et al [2] are part of a third wave of studies on pharyngeal nervous system function, and highlight the importance of detailed functional studies to understand the neural basis of behavior [7][8][9][10][11]. The authors combined laser ablation of specific neurons with newer tools, such as optogenetic stimulation and calcium imaging, to demonstrate that there are at least three independent circuits for inhibiting feeding, serving the function of the ''control circuit'' originally proposed by Albertson and Thomson [2].…”

“…Approaches that have shown promise include use of gene therapy with microbial opsins such as Chlamydomonas channelopsin to introduce light-regulated ion channels to inner retinal cells [3][4][5]; gene therapy to introduce the non-visual pigment melanopsin to the inner retina [6]; one-component and two-component optochemical photoswitches, which utilize light-isomerizable channel agonists to confer light sensitivity to remaining inner retinal photoreceptors [7][8][9]; and opto-electronic prostheses that stimulate retinal ganglion cells directly [10]. The latter approach is now approved in the US for clinical use.…”