Two novel forms of ERG oscillation inDrosophila: age and activity dependence

Abstract

Over an animal's lifespan, neuronal circuits and systems often decline in an inherently heterogeneous fashion. To compare the age-dependent progression of changes in visual behavior with alterations in retinal physiology, we examined phototaxis and electroretinograms (ERGs) in a wild-type D. melanogaster strain (Canton-S) across their lifespan. In aged flies (beyond 50% median lifespan), we found a marked decline in phototaxis, while motor coordination was less disrupted, as indicated by relatively stronger negative geotaxis. These aged flies displayed substantially reduced ERG transient amplitudes while the receptor potentials (RP) remained largely intact. Using a repetitive light flash protocol, we serendipitously discovered two forms of activity-dependent oscillation in the ERG waveforms of young flies: 'light-off' and 'light-on' oscillations. After repeated 500 ms light flashes, light-off oscillations appeared during the ERG off-transients (frequency: 50-120 Hz, amplitude: ∼1 mV). Light-on oscillations (100-200 Hz, ∼0.3 mV) were induced by a series of 50 ms flashes, and were evident during the ERG on-transients. Both forms of oscillation were observed in other strains of D. melanogaster (Oregon-R, Berlin), additional Drosophila species (D. funerbris, D. euronotus, D. hydei, D. americana), and were evoked by a variety of light sources. Both light-off and light-on oscillations were distinct from previously described ERG oscillations in the visual mutant rosA in terms of location within the waveform and frequency. However, within rosA mutants, light-off oscillations, but not light-on oscillations could be recruited by the repetitive light flash protocol. Importantly though, we found that both forms of oscillation were rarely observed in aged flies. Although the physiological bases of these oscillations remain to be elucidated, they may provide important clues to age-related changes in neuronal excitability and synaptic transmission.

Proteome-wide quantitative analysis of redox cysteine availability in the Drosophila melanogaster eye reveals oxidation of phototransduction machinery during blue light exposure and age

“…Thus, one limitation to our study is that we have not directly shown which phototransduction proteins are responsible for the ERG phenotype. Other groups have performed ERGs in old flies and observed decreased transient amplitudes [ 106 ], differing from our observations under blue light, consistent with the idea that the different phototransduction proteins identified as oxidized under each condition result in different physiological outcomes. Since we only measured glutathione ratios in the eye under light stress and aging, which is a limitation of our study, it is possible that there could be changes in the levels and/or localization of specific ROS under these two different conditions.…”

Distinct Aging-Vulnerable and -Resilient Trajectories of Specific Motor Circuit Functions in Oxidation- and Temperature-StressedDrosophila

“…In parallel, sev eral established behavioral assays have provided readouts of age-related functional decline, including fast phototaxis and negative geotaxis ( Miquel et al, 1976 ; Arking and Wells, 1990 ; Simon et al, 2006 ), flight ( Miller et al, 2008 ), memory ( Tamura et al, 2003 ; Yamazaki et al, 2007 ), courtship ( Cook and Cook, 1975 ; Partridge et al, 1987 ), as well as sleep and other circadian activity patterns ( Koh et al, 2006 ; Bushey et al, 2010 ). However, behavior-relevant studies registering concomitant changes in neurophysiological processes in Drosophila have been largely limited to electroretinogram ( Ueda et al, 2018 ), peripheral neuromuscular synapses ( Banerjee et al, 2021 ), or GF pathway SLR properties ( Martinez et al, 2007 ; Augustin et al, 2018 , 2019 ; Blagburn, 2020 ). Our work provides an initial glimpse across an array of motor circuits including the upstream processing of the GF-mediated escape circuit, and pattern generators driving flight and seizure discharges.…”