Neuroscience

eLife Assessment

In this valuable study, through carefully executed and rigorously controlled experiments, the authors challenged a previously reported role of the Death Receptor 6 (DR6/Tnfrsf21) in Wallerian degeneration (WD). Using two DR6 knockout mouse lines and multiple WD assays, both in vitro and in vivo, the authors provided convincing evidence that loss of DR6 in mice does not protect peripheral axons from WD after injury, at least in the specific contexts of the mice and analyses performed in this study. Due to the lack of certain specific parameters from previous studies (sex, age, mouse strains etc.), the exact reasons underlying the observed inconsistencies between current and previous reports on the protective effects of DR6 remains to be determined. Overall, this is a carefully executed study providing invaluable information toward understanding DR6's role (or lack thereof) in axon degeneration.

eLife Assessment

This important study characterizes a cascade of neural processes triggered by memory-based prediction errors. The study uses an impressive collection of approaches and methods to characterize and measure cognitive control, arousal, and memory changes as a function of memory-based violations. The analyses are technically sophisticated and rigorous and, taken together, provide solid evidence that there are multiple processes accompanying prediction errors, and that they differentially relate to successful encoding. The manuscript would be much improved by the addition of a discussion or visual schematic that integrates the numerous findings together into a more coherent model.

eLife Assessment

This computational study constitutes an extension to prior work on biophysical calcium-based synaptic plasticity rules with metaplasticity, investigating how single neurons can learn to perform non-linear pattern classification. This important work presents a significantly simpler solution to the studied problem with potentially broad applicability, there is however incomplete evidence to support the core conclusions.

eLife Assessment

This work presents a brain-wide atlas of vasopressin (Avp) and vasopressin receptor 1A (Avpr1a) mRNA expression in mouse brains using high-resolution RNAscope in situ hybridization. The single-transcript approach provides precise localization and identifies additional brain regions expressing Avpr1a, creating a valuable resource for the field. The revised manuscript is clearer and more impactful, with improved figures, stronger data organization, and enhanced scholarship through added context and citations. Overall, the evidence is compelling, and the atlas should be broadly of use to researchers studying vasopressin signaling and related neural circuits.

eLife Assessment

Recent studies have shown that mRNA can be acetylated (ac4c), altering mRNA stability and translation efficiency; however, the role of mRNA acetylation in the brain remains unexplored. In this important study, the authors demonstrate that ac4c occurs in synaptically localised mRNAs, mediated by NAT10. Conditional reduction of NAT10 protein levels led to decreases in ac4c of mRNAs and deficits in synaptic plasticity and memory. These solid results suggest that mRNA acetylation may play a role in memory consolidation.

eLife Assessment

This valuable study describes significant differences in prey capture behavior between PSD-95 knock-out and wild-type mice, despite prior work by the same authors showing only modest visual deficits in the former. The data convincingly demonstrated prey capture performance in PSD-95 knock-out mice to improve under monocular viewing conditions. However, this finding alone was inadequate to support the interpretation of results as revealing a deficit in binocular visual integration, especially given the lack of eye and head tracking data or consideration of alternative explanations for the observed behavior.

eLife Assessment

This manuscript details important findings that DNA polymerase kappa shows age-related changes in subcellular localization within different cell types in the brains of mice, from the nucleus in young cells to the cytoplasm in old cells. The authors' findings suggest that age-related alterations in POLK localization could drive mechanistic and functional changes in the aging brain. The authors provide solid evidence for their study, with data broadly supporting their claims with minor weaknesses.

eLife Assessment

Li et al. present an important and innovative study linking developmental changes in sleep to ecological context in Drosophila mojavensis, and propose that sleep at one stage of an animal's life might anticipate needs at a future stage. The results fit well with this model, but are correlative in nature. The work is convincing, scientifically rigorous, and effectively bridges sleep biology and evolutionary ecology, opening promising new directions for the field.

eLife Assessment

This important work employed a recent functional muscle network analysis to evaluate rehabilitation outcomes in post-stroke patients. While the research direction is relevant and suggests the need for further investigation, the strength of evidence supporting the claims is incomplete. Muscle interactions can serve as biomarkers, but improvements in function are not directly demonstrated, and the method's robustness is not benchmarked against existing approaches.

eLife Assessment

This important work introduces a splitGFP-based labeling tool with an analysis pipeline for the synaptic scaffold protein bruchpilot, with tests in the adult Drosophila mushroom bodies, a learning center in the Drosophila brain. The evidence supporting the conclusions is convincing.