Fig. 5. Cholinergic and serotonergic synapses are functionally disrupted in fat-3 mutant animals. (A-C) Synaptic release of endogenous serotonin was measured by determining the egg-laying response of fat-3(lg8101)/fat-3(qa1811) mutants to serotonin, fluoxetine and imipramine. Muscles are functional in fat-3 mutants because they respond well to serotonin (A,C). However, they are defective in serotonin release, because they respond only inefficiently to the endogenous serotonin potentiators fluoxetine (B) and imipramine (C). In C, a single dose of serotonin (5 mg/ml) and imipramine (0.75 mg/ml) were used. (D,E) Synaptic release of endogenous ACh was measured by determining the response to the endogenous ACh potentiator aldicarb. fat-3 mutants are defective in ACh release because aldicarb induces spastic paralysis faster in wild-type animals than in fat-3(lg8101)/fat-3(qa1811) (D) or in fat-3(wa22) (E) mutants. The defect of fat-3 mutants is weaker but comparable to that of rab-3(y250), a synaptic vesicle transmission mutant. ^*P<0.01; ^**P<0.005. (F) The altered aldicarb sensitivity of fat-3 mutants is of neuronal origin. fat-3 expressed in neurons, but not in muscles, restores normal aldicarb sensitivity to fat-3(lg8101) mutants. (GH) The ACh mimetic levamisole induces paralysis faster in fat-3(lg8101)/fat-3(qa1811) (G) and in fat-3(wa22) (H) mutants than in wild-type animals. ^*P<0.003. (I) Normal sensitivity to levamisole is restored in fat-3(lg8101)/fat-3(qa1811) mutant animals exposed to AA from egg to adult. In all panels, data points show the mean ± s.e.m.