Biology subjects

Turrel, O.

Publications and source records attributed to Turrel, O..

4 recordsLinked to original sources

bioRxiv2025

Active zone remodeling by Bruchpilot couples synaptic architecture to Kv1/Shaker excitability control

Presynaptic active zones are known to undergo state-dependent remodeling across sleep, circadian, and experience-dependent conditions, yet how such structural changes influence synaptic computation and excitability has remained unclear. Here, we address this gap by examining the functional consequences of physiological upscaling of the active zone scaffold Bruchpilot (BRP), within the range previously observed during natural state-dependent plasticity. We show that moderate BRP elevation expands the number of functional release sites while surprisingly reducing vesicle release probability, thereby establishing a presynaptic operating mode with selectively enhanced transmission at intermediate firing frequencies. This remodeled mode depends on Kv1/Shaker potassium channels, which normally constrain the increased structural capacity generated by BRP; accordingly, perturbation of Shaker abolishes BRP-dependent reductions in release probability and unmasks an enlarged synaptic output capacity. To test the functional relevance of this coupling, we examined sleepless mutants, in which Kv1/Shaker channels are destabilized and presynaptic remodeling is compromised. We show that direct, physiological-level BRP upscaling selectively restores the Shaker/Hyperkinetic channel complex from near-undetectable levels toward normal abundance without inducing global proteomic changes, and correspondingly rescues excitability balance, oxidative stress resistance, lifespan, and mid-term memory. Together, these findings identify a mechanistic coupling between active zone architecture and intrinsic excitability control and demonstrate how presynaptic structural plasticity shapes frequency-dependent transmission and functional robustness under stress.

neuroscience↗

bioRxiv2024

Cognitive hyperplasticity drives insomnia

Sleep is vital for maintenance of cognitive functions and lifespan across the animal kingdom. Here, we report our surprising findings that insomniac (inc) Drosophila short sleep mutants, which lack a crucial adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited excessive olfactory memory. Through a genetic modifier screen, we find that a mild attenuation of Protein Kinase A (PKA) signaling specifically rescued the sleep and longevity phenotypes of inc mutants. Surprisingly, this mild PKA signaling reduction further boosted the excessive memory in inc mutants, coupled with further exaggerated mushroom body overgrowth phenotypes. We propose that an intrinsic hyperplasticity scenario genuine to inc mutants enhances cognitive functions. Elevating PKA signaling seems to serve as a checkpoint which allows to constrain the excessive memory and mushroom body overgrowth in these animals, albeit at the sacrifice of sleep and longevity. Our data offer a mechanistic explanation for the sleep deficits of inc mutants, which challenges traditional views on the relation between sleep and memory, and suggest that behavioral hyperplasticity, e.g., prominent in autistic patients, can provoke sleep deficits.

neuroscience↗

bioRxiv2023

An antagonism between Spinophilin and Syd-1 operates upstream of memory promoting presynaptic long-term plasticity

We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here we show that an antagonism between two conserved regulatory proteins, Spinophilin (Spn) and Syd-1, controls presynaptic long-term plasticity and the maintenance of olfactory memories in Drosophila. While Spn mutants could not trigger nanoscopic active zone remodeling under homeostatic challenge and failed to stably potentiate neurotransmitter release, concomitant reduction of Syd-1 rescued all these deficits. The Spn/Syd-1 antagonism converged on active zone close F-actin, and genetic or acute pharmacological depolymerization of F-actin rescued the Spn deficits by allowing access to synaptic vesicle release sites. Within the intrinsic mushroom body neurons, the Spn/Syd-1 antagonism specifically controlled olfactory memory stabilization but not initial learning. Thus, this evolutionarily conserved protein complex controls behaviorally relevant presynaptic long-term plasticity, also observed in the mammalian brain but still enigmatic concerning its molecular mechanisms and behavioral relevance.

neuroscience↗

bioRxiv2021

Homeostatic active zone remodeling consolidates memories in the Drosophila mushroom body

Establishing a detailed understanding of how the distinct forms of synaptic plasticity spatio-temporally engage into the initial storage and subsequent consolidation of memories remains a fundamental challenge of neuroscience. In addition to the better understood postsynaptic plasticity, different forms of presynaptic plasticity are widely expressed in mammalian brains and apparently operate along Hebbian or homeostatic rules. Their behavioral relevance remains enigmatic, however. Lately, acute upregulation of active zone (AZ) scaffold protein BRP and release factor Unc13A via specific axonal transport factors were shown to mediate stable expression of presynaptic homeostatic plasticity (PHP) at Drosophila neuromuscular junctions (NMJs). We here demonstrate that AZ scaling processes are specifically needed for stable expression of both, NMJ PHP as well as aversive olfactory mid-term memory within intrinsic neurons of the Drosophila mushroom body (MB). We first demonstrate that AZ upscaling via BRP is specifically needed for expression but not induction of NMJ homeostatic plasticity, thus establishing a direct temporal plasticity sequence of molecularly distinct AZ remodeling steps. Notably, when we reduced BRP and associated transport factors in MB intrinsic neurons, short-term memory persisted but robust deficits in stable memory expression for a few hours after conditioning were observed. In contrast, AZ release site protein RIM-BP affecting PHP induction was additionally needed for successful formation of short-term memory. Taken together, our data establish a specific role of homeostatic presynaptic long-term plasticity for memory consolidation. Such homeostatic refinement processes might well be needed to successfully integrate and display synaptic engrams constituting intermediary term memories.

neuroscience↗