Biology subjects

Escher, M.

Publications and source records attributed to Escher, M..

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↗

bioRxiv2025

Fine-scale animal proximity detection and localization via multi-sensor biologgers

O_LIAccurately quantifying spatial interactions is central to understanding social behavior, information flow, predator-prey dynamics, and disease transmission. Proximity loggers that record received signal strength indicator (RSSI) offer a promising approach for estimating pairwise distances, particularly in environments where GPS is unavailable or imprecise. However, RSSI is often dismissed as too noisy for fine-scale inference, with performance that depends on environmental conditions, tag orientation, and between-device variability. Incorporating additional tag-measured data may improve RSSI performance and enable its use as a continuous measure of distance in variable environments. C_LIO_LIHere, we assess the utility of continuous RSSI as a fine-scale distance estimator and localization tool using a novel multi-sensor WiFi biologger (WildFi). We conducted four experiments: (1) testing how tag orientation affects RSSI-distance relationships; (2) evaluating whether environmental covariates measured by onboard sensors improve proximity estimates; (3) assessing the accuracy of trilateration-based tag localization using fixed gateway arrays; and (4) comparing RSSI- and GPS-inferred proximity in free-ranging Egyptian fruit bats (Rousettus aegyptiacus). C_LIO_LIWhile RSSI alone could predict distance with reasonable accuracy, incorporating additional tag-sensed information (e.g., temperature, humidity, barometric pressure) and accounting for tag-level heterogeneity significantly improved predictive accuracy. Based on RSSI predictions, we could estimate tag location with a median error of 2.6 meters, accurate enough to indirectly estimate proximity networks without tag-to-tag communication. In deployments on free-flying bats, we found that RSSI and GPS were only weakly concordant, with GPS unreliable for detecting fine-scale interactions (<50 m). In contrast, RSSI could capture both fine-scale and some long-range interactions up to [~]250m. C_LIO_LIThese findings highlight RSSIs potential as a robust metric for proximity logging, particularly when combined with multi-sensor data and pre-deployment validations. Integrating multi-sensor data streams further enhances RSSI interpretability. Future biologger designs should prioritize synergy among data streams for integrated insights into proximity and animal behavior. C_LI Data and code for peer review statementData and code to reproduce the results of the paper are provided in a zip folder for peer review. We also provided our compiled code.

ecology↗

bioRxiv2025

An active Unc13A is Reboundless in sleep homeostasis

One of the major characteristics of sleep is homeostatic sleep rebound following sleep loss. While the molecular mechanisms of baseline sleep regulation have been intensively studied, a specific molecular understanding of sleep rebound remains elusive. Here, we show that a constitutively active form of the Munc13-family presynaptic release factor Unc13A, which lacks the inhibitory Ca2+/calmodulin interaction domain (Unc13AWRWR), dominantly suppressed sleep rebound upon acute sleep deprivation, leading to a nearly complete elimination of recovery sleep ("reboundless"). In contrast, baseline sleep remained largely normal. Through a genetic modifier screen, we found that this dominant "reboundless" phenotype of Unc13AWRWR was rescued by a partial loss of Snap, a cofactor of NSF required for disassembly and recycling of post-fusion cis-SNARE complex. Given that Unc13A promotes fusion-competent trans-SNARE complex formation, these findings suggest that sleep rebound may depend on a delicate balance between SNARE complex assembly and recycling. Additionally, we found that expression of a human disease-associated active Unc13A (Unc13APL) variant attenuated baseline and rebound sleep. Since both Unc13AWRWR and Unc13APL were shown to promote presynaptic release probability (Pr), we speculate that Unc13A suppresses recovery sleep likely by increasing Pr and subsequently enhancing synaptic transmission, probably through elevated trans-SNARE formation and efficient cis-SNARE recycling. Taken together, our data demonstrate a fundamental role of Unc13A and SNARE dynamics in sleep homeostasis.

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↗