Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit

Abstract

Serotonin (5-HT) modulates synaptic efficacy in the nervous system of vertebrates and invertebrates. In the nematode Caenorhabditis elegans, many behaviors are regulated by 5-HT levels, which are in turn regulated by the presence or absence of food. Here, we show that both food and 5-HT signaling modulate chemosensory avoidance response of octanol in C. elegans, and that this modulation is both rapid and reversible. Sensitivity to octanol is decreased when animals are off food or when 5-HT levels are decreased; conversely, sensitivity is increased when animals are on food or have increased 5-HT signaling. Laser microsurgery and behavioral experiments reveal that sensory input from different subsets of octanol-sensing neurons is selectively used, depending on stimulus strength, feeding status, and 5-HT levels. 5-HT directly targets at least one pair of sensory neurons, and 5-HT signaling requires the G␣ protein GPA-11. Glutamatergic signaling is required for response to octanol, and the GLR-1 glutamate receptor plays an important role in behavioral response off food but not on food. Our results demonstrate that 5-HT modulation of neuronal activity via G protein signaling underlies behavioral plasticity by rapidly altering the functional circuitry of a chemosensory circuit.A t the level of individual synapses, plasticity usually refers to changes in efficacy of synaptic transmission. However, at the scale of a neural network, this plasticity translates to changes in functional circuitry. The 302 neurons of the Caenorhabditis elegans nervous system are largely invariant in their location and lineage, and the overall pattern of synaptic connections between classes of neurons is similar in multiple animals (1). With limited variability in synaptic connectivity, behavioral plasticity in C. elegans likely occurs by differential utilization of existing synaptic connections, rather than de novo synaptogenesis.The biogenic amine serotonin (5-HT) modulates synaptic efficacy in vertebrates and invertebrates. For example, 5-HT modulates both locomotor reflex and nociception in the rat spinal cord (2, 3). In cultured Aplysia neurons 5-HT is critical for both short-term and long-term changes in synaptic efficacy (4, 5). In humans, defects in 5-HT signaling are implicated in behavioral disorders, including depression, bulimia, obsessivecompulsive disorder, and alcoholism (6). Although drugs that increase synaptic 5-HT levels such as fluoxetine (i.e., Prozac) are often used to treat these conditions, very little is known about how altering 5-HT levels causes changes in functional circuitry or behavior.Several lines of evidence suggest that in C. elegans, high levels of 5-HT signal the presence of food. In the presence of food (Escherichia coli is used as a food source in the laboratory), pharyngeal pumping (7, 8), egg laying (8, 9), and male mating (10) are increased, whereas locomotion is decreased (11). Conversely, in the absence of food, the opposite behaviors are observed. The effect of food on these behaviors can largely be...

Generation and modulation of chemosensory behaviors in C. elegans

“…Fifth, to further emphasize the importance of avoiding noxious chemicals, the ability to sense noxious chemicals is largely segregated from the ability to respond to attractive chemicals at the level of the sensory neurons themselves (Table 1). Thus, the ASH, ADL, and AWB neurons mediate aversive behaviors more or less exclusively, whereas attraction is mediated by the remaining eight pairs of amphid chemosensory neurons [58, 65,71,72,[89][90][91]. This organization is similar to observations in the mammalian and Drosophila gustatory system, where sensory cells responding to sugars and other palatable compounds are segregated from those sensing bitter and hence, toxic compounds [92][93][94][95][96][97].…”

“…Thus, the ASH, ADL, and AWB sensory neuron types, which are the primary sensors of toxic chemicals or nociceptive stimuli, synapse directly onto backward command interneurons that direct backward locomotion via activation or inhibition of motor neurons [53] (Fig. 1a), enabling the worm to execute a rapid and robust escape response when these neurons are activated [63][64][65]. On the other hand, neurons that sense attractive chemicals synapse onto intervening layers of interneurons.…”

“…The presence or absence of food can rapidly and reversibly alter the responses of animals to the volatile repellent 1-octanol, and this modulation may occur presynaptically via serotonergic signaling [65]. In another behavioral paradigm, animals are presented simultaneously with an attractive odorant such as diacetyl, and a repellent chemical such as Cu 2+ ions.…”

Requirement of the RNA-editing Enzyme ADAR2 for Normal Physiology in Mice

“…The alterations observed in PPI indicate a change in sen-sorimotor integration, hence changes in brain function, which might be caused by differences in any of several neurochemical systems (29). The 5-HT2C serotonin receptor, a known ADAR2 substrate (30), modulates sensory responses in C. elegans by acting directly on sensory neurons (31). Changes in this receptor signaling may be related to the PPI deficit identified in the ADAR2 KO mice.…”

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

“…Notably, the neurotransmitters, such as neuropeptides, serotonin (5-HT), tyramine (TA) and octopamine (OA), have been increasingly shown to be transmitters or modulators of ASH-mediated aversive behaviours [12][13][14][15] . ASI sensory neurons are reported to mediate dauer formation 16 , enable worms to learn to avoid the smell of pathogenic bacteria after ingestion via INS-6 signalling 17 , suppress male-specific sexual attraction behaviour 18 , respond to temperature stimuli to negatively modulate thermotaxis behaviour 19 , mediate diet-restriction-induced longevity 20 , modulate satiety quiescence 21 , regulate acute CO 2 avoidance 22 , repress exploratory behaviours that comprise spontaneous reversals and omega turns 5 , and inhibit ASH-mediated aversive responses to 100% 1-octanol 23 . These studies support the hypothesis that ASIs are important polymodal sensory neurons mediating or modulating worm behaviours and development.…”