Drosophila melanogaster

Memory decline with aging is a common phenomenon in animals, including humans, but the mechanism has not yet been elucidated. In our laboratory, we use Drosophila, which has relatively simple neural circuits, as a model animal to elucidate the mechanism by which aging causes memory decline. In particular, by identifying the neural circuits and risk factors that cause memory loss associated with aging, we hope to elucidate one aspect of the mechanism of memory loss and propose a new approach to drug discovery.

1. identification of neural circuits responsible for memory decline associated with aging

　 The effects of aging differ depending on the type of memory. In humans, it is generally known that long-term memory is more susceptible to the effects of aging than short-term memory. In flies, it has become clear that olfactory memory, which is formed by associative learning of odors and electrical stimuli, is more susceptible to the effects of aging in the mid-term memory and part of the long-term memory than in the short-term memory. In order to understand the effects of aging on different types of memories, we are analyzing changes in neural activity before and after olfactory memory learning by in vivo calcium imaging using a genetically encoded Ca2+ sensor (GCaMP), and comparing the results between young and old individuals to identify neural circuits that are impaired with aging. We are also working on the identification of temperature-sensitive cation channels. In addition, thermogenetics, which uses flies expressing neuron-specific genes that block temperature-sensitive cation channels and synaptic transmission, can be used to activate or block specific neurons in a time-specific manner. Using this method, we aim to analyze the effects on memory formation by artificially activating or blocking neural circuits that are impaired with aging, and to identify the neural circuits that control memory decline with aging. 2.

2) Identification of risk factors that cause memory loss associated with aging

　 Aging changes various functions in the body. Decline of metabolic function in vivo is one of them and is considered as a risk factor that affects memory function, but the mechanism is not clear. Using the fly olfactory memory as a model system, we are genetically manipulating the decline of metabolic mechanisms in vivo due to aging and evaluating and analyzing the effects on neural and molecular networks. In addition, we aim to identify the genetic profiling of age-related changes in the brain or in specific neuronal populations by transcriptome analysis, with the aim of comprehensively identifying risk factors that cause memory loss associated with aging.