2002 East Coast Worm Meeting abstract 40
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
| 1 | Dept. of Pathology, Harvard Medical School |
| 2 | MGH Cancer Center, 149-7202 13th St., Charlestown, MA 02129 |
| 3 | Takeda Chemical Industries, Ltd., Ibaraki 300-4293, Japan |
C. elegans responds to the volatile repellant 1-octanol by moving backwards. To study this chemosensory response we screened for mutants that do not respond to octanol, and found that a subset of the mutants obtained were defective only in the absence of food. Because the presence of food is thought to increase serotonin (5-HT) signaling, we investigated whether 5-HT is involved in this food-dependent regulation of octanol detection. Exogenous 5-HT restores the ability to respond to octanol in the absence of food in most of these mutants. Furthermore, at least two of these mutants were also partially resistant to 5-HT-induced paralysis, suggesting that they may be defective in 5-HT signaling in motor neurons as well. Because eat-4 animals (which are defective for glutamatergic signaling) are mutant for octanol avoidance, but tph-1 animals (which lack 5-HT biosynthesis) and dgk-1 animals (which are defective for 5-HT signaling) are only defective in detecting dilute octanol, our results suggest that 5-HT modulates glutamatergic signaling in this circuit. We are currently further characterizing these mutants in the hope of identifying genes involved in 5-HT modulation of synaptic signaling.
We investigated the roles of ASH and ADL, two amphid sensory neurons previously found to be important for responding to octanol (1), in this food-dependent modulation. Laser ablation experiments revealed that ASH is the primary sensory neuron in the presence of food, while ASH and ADL contribute equally in the absence of food. Exogenous 5-HT largely mimicked the presence of food, providing further evidence that 5-HT directly modulates synaptic activity in this circuit. In one possible scenario 5-HT could inhibit octanol detection in ADL, resulting in only ASH being active on food; however, in tph-1 animals, ablation of ASH results in a strong defect in octanol avoidance both on and off food, indicating that ADL is inactive even in the absence of 5-HT biosynthesis. Therefore, we propose an alternative model in which "silent synapses" between ADL and command interneurons are silent when 5-HT is absent, inhibited at high levels of 5-HT (i.e., when animals are well-fed), and become active when 5-HT levels drop below a certain threshold (i.e., when animals are starved). This is reminiscent of silent glutamatergic synapses in the rat spinal cord dorsal horn, in which synapses are active at low levels of 5-HT but are silent when 5-HT levels are absent or high (2). Our data suggest a possible conserved cellular mechanism by which 5-HT could modulate sensitivity in the nervous system.
References:
(1) Troemel et al. (1995). Cell 83:207-
(2) Li and Zhuo (1998). Nature 393:695-