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 Galpha 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.

Fig. 2.

5-HT modulates signaling of ASH neurons via gpa-11.(A) Role of ASH neurons on response to 30% octanol on or off food. ***, P < 0.001 (vs. control off food). (B) Effect of mutating gpa-11 on response to 30% octanol. **, P < 0.01; ***, P < 0.001.

Fig. 1.

Food and 5-HT modulate response to diluted octanol. Data are presented as mean time to respond to octanol ±SEM. (A) Dose–response curves of WT, tph-1, and mod-5 animals to octanol. n ≥ 18 for each data point. (B) Effect of food and 5-HT on response to diluted octanol. **, P < 0.01.

Fig. 3.

Food modulates response to 100% octanol. Data are presented as mean time to respond to octanol ±SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Fig. 4.

Precise 5-HT levels are critical for modulation of response to 100% octanol. (A) Response of 5-HT-treated, ASH-killed WT animals, and ASH-killed tph-1 animals. Data are presented as mean time to respond to octanol ±SEM. (B) Effect of exogenous 5-HT on the response to 100% octanol in ASH-killed tph-1 animals. Data are presented as mean time to respond to octanol ±SEM. ***, P < 0.001.

Fig. 5.

glr-1, but not gpa-11, plays a role in the response to 100% octanol off food. Data are presented as mean time to respond to octanol ±SEM. Columns 1–8 are duplicated from Figs. 3 and 4A for qualitative comparison purposes only. Control animals underwent mock laser microsurgery in parallel with their respective experimental groups. ***, P < 0.001.

Fig. 6.

Model for food and 5-HT modulation of the octanol response circuit. (A) Animals on food respond robustly to 30% octanol. The presence of food likely leads to increased 5-HT levels, which increases the sensitivity of ASH neurons via a gpa-11-dependent mechanism. (B) Animals off food respond poorly to 30% octanol, probably because of decreased 5-HT levels and decreased gpa-11 signaling. However, any residual response to 30% octanol is still mediated only by ASH neurons. (C) Animals on food respond to 100% octanol via ASH neurons only. High levels of 5-HT inhibit signaling through ADL and AWB neurons, although it is unclear whether 5-HT is acting presynaptically or postsynaptically in this case. glr-1 is not required for response on food, suggesting that another glutamate receptor is sufficient for response. gpa-11 does not play a major role in response to 100% octanol on food. (D) Animals off food respond to 100% octanol off food via ASH, ADL, and AWB neurons. The lowered 5-HT levels slightly decrease signaling through ASH neurons, but increase signaling through ADL and AWB neurons. glr-1 plays an important role in response to 100% octanol off food.