Worm Breeder's Gazette 13(3): 79 (June 1, 1994)
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.
Adaptation, the process by which a response becomes attenuated or inhibited after prolonged stimulation, is critical to a variety of processes involving the nervous system, including addiction, information processing and learning. We have been investigating the molecular and cellular basis of adaptation in the C. elegans nervous system by isolating and characterizing mutations that cause defects in adaptation to neuroactive drugs. One mutant we have found, unc-2 ( mu74 ),fails to adapt to paralysis and egg-laying inhibition by dopamine. The unc-2 ( mu74 )mutant is not hypersensitive dopamine, however, indicating that unc-2 ( mu74 )is specifically defective in adaptation, not response, to dopamine. unc-2 ( mu74 )has a number of other behavioral phenotypes, most of which are phenocopied by serotonin treatment. unc-2 ( mu74 )animals also fail to adapt to paralysis by serotonin, and are hypersensitive to serotonin's effects on egg-laying, suggesting that unc-2 ( mu74 )may be defective in regulating serotonin response or release. The constellation of phenotypes seen in unc-2 ( mu74 ),including failure to adapt to dopamine, are also observed in other alleles of unc-2 ,including the canonical allele e55 .Interestingly, one allele, e2379 ,has only a subtle adaptation defect, although it exhibits most other unc-2 phenotypes. This suggests that the diverse phenotypes of unc-2 may result from actions of unc-2 in multiple pathways, perhaps in multiple cell types. We are currently attempting the discern the cellular basis of the unc-2 ( mu74 )phenotype through mosaic analysis.
Because the unc-2 ( mu74 )mutation was generated with psoralen, we were able to clone unc-2 by identifying a small, closely linked deletion present in the unc-2 ( mu74 )strain. Injection of the cosmid containing this deletion conferred partial rescue of unc-2 ( e55 )in the F1 progeny of injected animals. Partial genomic sequence revealed that unc-2 encodes a protein with high sequence similarity to the alpha-1 subunit of N-type calcium channels. The unc-2 ( mu74 )strain contained a 100 bp. deletion that removed 50 bp of coding sequence and a predicted splice donor site; the mutant gene would therefore not be expected to encode a functional channel. We are presently determining the sequence alterations of other unc-2 alleles.