The negative-geotaxis climbing assay is used to efficiently study aging and neurodegeneration in Drosophila.To make it suitable for large-scale study,a method called the rapid iterative negative geotaxis（RING） assay has been established by simultaneously photographing the climbing of multiple groups of flies when they are manually tapped down in test tubes.Here,we automated the assay by using a well-controlled electric motor to drive the tapping,and a homemade program to analyze the climbing height of flies.Using the automated RING（aRING） assay,we found that the climbing ability of a strain of wild-type flies,males in particular,declined rapidly before day 21 after eclosion,but slowly from day 21 to 35.We also found that the expression of arctic mutant Aβ_（42） accelerated the age-dependent decline in the climbing ability of flies.Moreover,using aRING,we examined the effect of third chromosome deficiencies on the accelerated locomotor decline in Aβ_（42）-expressing flies,and isolated 7 suppressors and15 enhancers.
Beta amyloid （Aβ42）-induced dysfunction and loss of synapses are believed to be major underlying mechanisms for the progressive loss of learning and memory abilities in Alzheimer＇s disease （AD）. The vast majority of investigations on AD-related synaptic impairment focus on synaptic plasticity, especially the decline of long-term potentiation of synaptic transmission caused by extracellular Aβ42. Changes in other aspects of synaptic and neuronal functions are less studied or undiscovered. Here, we report that intraneuronal accumulation of Aβ42 induced an age- dependent slowing of neuronal transmission along pathways involving multiple synapses.
