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Metallothioneins (MTs) have the potential to a variety of physiological processes, including neurobehavioral development, and cognitive functions.Here we further show that MTL-1 and MTL-2, metallothionein proteins, participate in the sensory integration control in Caenorhabditis elegans.The mtl-1 and mtl-2 mutants showed deficits in the integration of two sensory signals, and normal associative learning behaviors.Animals over-expressing MTL-1 and MTL-2 exhibited the similar phenotype of sensory integration to wild-type.MTL-1 and MTL-2 are not necessary for the development of nervous system, but they may function in the regulation of mature neuronal circuit.Moreover, besides exclusively expressing in intestinal cells, expressing MTL-1 and MTL-2 in nervous system and AIY interneurons rescued the sensory integration deficits in mtl-1 and mtl-2 mutants, respectively.Mutations of mtl-1 and mtl-2 decreased the integration of sensory signals in mutants of hen-1 and ttx-3, which are required to regulate the sensory integration in AIY interneurons.Furthermore, expression of MTL-1 and MTL-2 partially rescued the interaction deficits in hen-1 and ttx-3 mutants.Thus, MTs may regulate sensory integration in the mature neuronal circuit though influencing the functions of interneurons.