Miniature neurotransmission is required to maintain Drosophila synaptic structures during ageing

Abstract

The decline of neuronal synapses is an established feature of ageing accompanied by the diminishment of neuronal function, and in the motor system at least, a reduction of behavioural capacity. Here, we have investigated Drosophila motor neuron synaptic terminals during ageing. We observed cumulative fragmentation of presynaptic structures accompanied by diminishment of both evoked and miniature neurotransmission occurring in tandem with reduced motor ability. Through discrete manipulation of each neurotransmission modality, we find that miniature but not evoked neurotransmission is required to maintain presynaptic architecture and that increasing miniature events can both preserve synaptic structures and prolong motor ability during ageing. Our results establish that miniature neurotransmission, formerly viewed as an epiphenomenon, is necessary for the long-term stability of synaptic connections.

Botulinum neurotoxin accurately separates tonic vs phasic transmission and reveals heterosynaptic plasticity rules in Drosophila

“…One promising approach to electrophysiologically separate MN-Is and MN-Ib would be to employ a conditional null allele of the vesicular glutamate transporter ( vGlut ) that was recently developed (Banerjee et al, 2021; Sherer et al, 2020). In principle, this would be an ideal approach because all glutamate release would be silenced without otherwise perturbing innervation or synaptogenesis.…”

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.…”

“…In Drosophila, characteristic declines over the life span have been documented in motor coordination ( Leffelaar and Grigliatti, 1983 ; Gargano et al, 2005 ) and in higher functions, such as learning and memory ( Tamura et al, 2003 ; Yamazaki et al, 2007 ). However, fewer studies have directly assessed cellular physiological decline underlying changes in behavioral performance across the life span ( Martinez et al, 2007 ; Banerjee et al, 2021 ). It is important, therefore, to identify the neural circuits and associated behavioral outputs that are prone to age-related modifications and determine whether specific neuronal elements are differentially vulnerable in this process.…”

A conditional glutamatergic synaptic vesicle marker forDrosophila

“…Primary antibodies and dilution factors: The SYN (3C11) mAb 1:25 developed by E. Buchner ( Klagges et al 1996 ) was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. Mouse anti-vGlut ( Banerjee 2021 ) 1:10; Rabbit anti-Syt ( Littleton et al 1993 ) 1:1,000; Mouse anti-mCherry (Biorbyt orb256058) 1:200; Rabbit anti-mCherry (Abcam ab213511) 1:500, Rabbit Abfinity anti-GFP (Thermo-Fisher) 1:400, Rabbit anti-HA (Cell Signaling C29F4) 1:500, and Rat anti-FLAG (Novus NBP1-06712) 1:200. Secondary antibodies and dilution factors: Donkey anti-Rat Alexa 488 (Jackson Immunoresearch 712-546-153) 1:400, Donkey anti-Mouse Alexa 488 (Jackson Immunoresearch 715-545-151) 1:400, Goat anti-Rabbit Alexa 488 (Thermo-Fisher A32731) 1:200, Donkey anti-Mouse JF549 (Novus NBP1-75119JF549) 1:200, Goat anti-Rabbit JF549 (Novus NBP1-72732JF549) 1:200, Goat anti-Rabbit JF646 (NBP1-72732JF646).…”