Sensory neurons can be divided into two groups, neurons like photoreceptor cells that normally detect one type of stimulus and neurons that respond to more than one type or mode of stimulation- polymodal neurons. Laser ablation studies by various researchers demonstrated that the ASH polymodal sensory neurons are primarily responsible for the detection of varied stimuli including nose touch, high osmolarity and volatile repellents (WBG 10(1):89, CGC 1705, 2314). C. elegans can distinguish between nose touch and other stimuli detected by ASH; habituation to nose touch eliminates 60% of the response to nose touch- but leaves intact response to high osmolarity and volatile repellents. We are interested in learning both how these stimuli are detected and how animals distinguish between them. The ASH neurons express both putative mechanoreceptors and chemoreceptors: DEG-1, R13A1.4,
sra-6 and
srb-6 (WBG 14(2):90, CGC 1299, 2314). However, neither null alleles of the
deg-1 nor mec mutations perturb response to stimuli detected by ASH. We have identified mutations that specifically prevent either nose touch response or high osmolarity avoidance and we plan to screen for mutations that perturb response to volatile repellents. We are currently cloning and characterizing
osm-10, which may encode an osmoreceptor. Isolated by J. Thomas (WBG 10(3):167),
osm-10(
n1602)III animals are severely defective in their response to high osmolarity, yet they respond normally to the other stimuli detected by ASH. 3+/-1% of N2 animals escape an 8M glycerol barrier after 10 minutes, but 77+/-5% of
n1602 animals escape. The
osm-10 gene maps between
mec-14 and
lin-39 and was identified based on phenotypic rescue. The predicted protein product is 419 amino acids long with a putative transmembrane domain and shows no significant identity to previously identified proteins. The
n1602 mutation causes the substitution of a lysine for a glutamic acid in the putative extracellular domain. Although
n1602 acts as a null allele in genetic tests, it may correspond to a partial loss of function. Insertions of the GFP coding sequence in the rescue construct eliminate
osm-10 rescue activity, but the resulting reporter constructs consistently have GFP expression in four classes of sensory neurons: ASH, ASI, PHA and PHB. All four classes of neurons have exposed, ciliated, sensory endings (ASH and ASI in the anterior; PHA and PHB in the posterior). Previous work has demonstrated a minor role for ASI in chemosensation, but the no sensory stimuli detected by the PHA and PHB neurons have been identified. Laser ablation experiments are forthcoming, but the synaptic targets of PHB neurons suggest that they could evoke a change in locomotion in response to high osmolarity. The targets of PHB include the backward command interneurons, AVA and AVD, and the forward command interneuron PVC (CGC 765); the primary synaptic target of PHA is PHB. If PHA or PHB detects high osmolarity, then PHB may release an inhibitory neurotransmitter and evoke forward locomotion. ASH may evoke backward locomotion by excitation of its synaptic targets which include AVA, AVD and AVB (the other forward command interneuron). (CGC 2308, 2309). The predicted expression pattern of
osm-10 suggests that it is directly involved in osmotic detection. OSM-10 probably interacts with other proteins to form a functional osmoreceptor. The
nu288 IV mutation noncomplements
n1602 III and may encode another subunit of the receptor complex. We plan to identify and characterize additional mutations which noncomplement
n1602, in addition to further analysis of
osm-10. Genetic and molecular analysis of this circuit will reveal the molecules involved in stimulus detection and discrimination. In the future these techniques will be complemented by an eletrophysiological analysis of the neurons in this polymodal circuit (CGC 2254).