Aberrant neuronal hyperactivation causes an age- and diet-dependent decline in associative learning behavior

The impairment of memory, cognition, and behavior during aging is generally thought to arise from diminished neuronal activities. The nematode Caenorhabditis elegans exhibits age-dependent declines in an associative learning behavior called thermotaxis. Genetic ablation of individual neurons revealed that an absence of either AWC sensory or AIA inter-neurons preserved the thermotaxis ability of aged animals. Calcium imaging showed age-dependent spontaneous hyperactivities in both neurons. The age-dependent neuronal hyperactivity and behavioral decline were ameliorated by changing diets. We further demonstrate that the enhanced activities of AWC and AIA were differentially dependent on the forms of neurotransmission mediated by neurotransmitters and neuropeptides. Together, our data provides evidence that aberrantly enhanced, not diminished, neuronal responses can impair behavior during aging. One-Sentence Summary Enhanced neuronal activity during aging impairs C. elegans learning behavior.