Molecular Remodeling of the Presynaptic Active Zone of Drosophila Photoreceptors via Activity-Dependent Feedback

Sugie, Atsushi; Hakeda-Suzuki, Satoko; Suzuki, Emiko; Silies, Marion; Shimozono, Mai; Möhl, Christoph; Suzuki, Takashi; Tavosanis, Gaia

doi:10.1016/j.neuron.2015.03.046

Cited by 86 publications

(146 citation statements)

References 84 publications

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“…To do this, we used the STaR ( S ynaptic Ta gging with R ecombination) system (Chen et al, 2014), which enables labeling of active zones specifically within a defined circuit, by tagging native Bruchpilot (BRP) in a FLP/FRT dependent manner. Changes in BRP levels are a key mechanism underlying activity-dependent plasticity in adult neurons (Sugie et al, 2015), and changes in synaptic structure, and both number and size of active zones in particular, are generally associated with changes in synaptic strength (Holderith et al, 2012; Weyhersmuller et al, 2011). Two hours after mechanical sleep deprivation had ended, BRP signal in the R2 ring structure was significantly increased in sleep-deprived flies compared to rested control flies (Figures 4A-4C), and this greater BRP signal was due to increases in both the number and size of BRP puncta in the R2 ring (Figure 4D).…”

Section: Resultsmentioning

confidence: 99%

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit

Liu

Tabuchi

et al. 2016

Cell

303

477

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Summary Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca2+ levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting these EB neurons undergo “sleep need”-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes within this circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive.

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Section: Resultsmentioning

confidence: 99%

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit

Liu

Tabuchi

et al. 2016

Cell

303

477

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“…Recent studies support that synaptic and network activity contribute to active zone protein turnover (Lazarevic et al, 2011; Sugie et al, 2015; Weyhersmüller et al, 2011). It is thus possible that loss of synaptic activity in the cultured neurons contributes to the strong active zone disruption that we observe upon RIM/ELKS deletion.…”

Section: Discussionmentioning

confidence: 97%

Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking

Wang

Held

Wong

et al. 2016

Neuron

135

218

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In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected. Despite loss of the priming proteins Munc13 and RIM and of docked vesicles, a pool of releasable vesicles remained. Thus, the active zone is necessary for synaptic vesicle docking and to enhance release probability, but releasable vesicles can be localized distant from the presynaptic plasma membrane.

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“…Our observations demonstrate an illumination-dependent remodeling of dynamin1xb at the mouse photoreceptor ribbon synapse that most likely affects endocytic vesicle trafficking in the peri-active zone. Interestingly, in drosophila, an illumination-dependent reorganization also of the active zone of photoreceptor synapses was described (Böhme and Sigrist, 2015; Sugie et al, 2015). The detailed molecular mechanisms of these adaptative processes in retinal synapses have to be addressed by future investigations.…”

Section: Discussionmentioning

confidence: 99%

The Calcineurin-Binding, Activity-Dependent Splice Variant Dynamin1xb Is Highly Enriched in Synapses in Various Regions of the Central Nervous System

Eich

Dembla

Wahl

et al. 2017

Front. Mol. Neurosci.

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In the present study, we generated and characterized a splice site-specific monoclonal antibody that selectively detects the calcineurin-binding dynamin1 splice variant dynamin1xb. Calcineurin is a Ca2+-regulated phosphatase that enhances dynamin1 activity and is an important Ca2+-sensing mediator of homeostatic synaptic plasticity in neurons. Using this dynamin1xb-specific antibody, we found dynamin1xb highly enriched in synapses of all analyzed brain regions. In photoreceptor ribbon synapses, dynamin1xb was enriched in close vicinity to the synaptic ribbon in a manner indicative of a peri-active zone immunolabeling. Interestingly, in dark-adapted mice we observed an enhanced and selective enrichment of dynamin1xb in both synaptic layers of the retina in comparison to light-adapted mice. This could be due to an illumination-dependent recruitment of dynamin1xb to retinal synapses and/or due to a darkness-induced increase of dynamin1xb biosynthesis. These latter findings indicate that dynamin1xb is part of a versatile and highly adjustable, activity-regulated endocytic synaptic machinery.

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Molecular Remodeling of the Presynaptic Active Zone of Drosophila Photoreceptors via Activity-Dependent Feedback

Cited by 86 publications

References 84 publications

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit

Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking

The Calcineurin-Binding, Activity-Dependent Splice Variant Dynamin1xb Is Highly Enriched in Synapses in Various Regions of the Central Nervous System

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