Neuroscience

eLife assessment

This valuable study further discloses the function of LRRK2 in BDNF-dependent synaptic processes in identifying postsynaptic actin cytoskeleton as a convergent site of LRRK2 pathophysiological activity. Multiple approaches in different cellular models provide mostly solid (but at times preliminary) evidence to support (many) of the conclusions, overall consistent with bioinformatics analyses covering previously published work. While an exciting start that should be pursued, examples are suggested by reviewers to add in additional experimentation to better support the expansive interpretation. The identification of mechanisms of LRRK2 action at the synapse is considered highly significant, as better knowledge in this regard may provide insight into why dopaminergic cells die with over-active LRRK2.

eLife assessment

This valuable study by Bartas and colleagues examined how patterns of monosynaptic input to specific cell types in the ventral tegmental area are altered by drugs of abuse. The authors applied a dimensionality reduction approach (principal component analysis) and showed that various drugs of abuse, and somewhat surprisingly the anesthesia alone (ketamine/xylasin), caused changes in the distribution of inputs labeled by the transsynaptic rabies virus. While there are some issues to be addressed, the evidence supporting the conclusions is overall solid, and provides information that is of value to the field, as well as a cautionary note on the interpretation of rabies virus-based tracing experiments.

eLife assessment

This study describes important findings related to early disruptions in disinhibitory modulation exerted by VIP+ interneurons, in CA1 in a transgenic model of Alzheimer's disease pathology. The authors provide a convincing analysis at the cellular, synaptic, network, and behavioral levels on how these changes correlate and might be related to behavioral impairments during these early stages of AD pathology.

eLife assessment

This valuable study presents new observations on white matter organisation at the micron scale, using a combination of synchrotron imaging and diffusion MRI across two species. Notably, the authors provide solid evidence for the fasciculation of axons within major fibre bundles into laminar structures, though these structures are not consistently observed across modalities or species. The study will be of general interest to neuroanatomists and those interested in white matter imaging.

eLife assessment

This study convincingly demonstrates the ability of reverting a neurodevelopmental defect with a dietary intervention. While the exact mechanisms remain to be elucidated, the authors establish a simple but important system to study the PI3K/Akt/FOXO pathway but also the action of ketone bodies and their potential therapeutic use. This study will be of particular interest to the large community of scientists studying E/I disequilibrium in the nervous system.

eLife assessment

The study presents an important ecosystem designed to support literature mining in biomedical research, showcasing a methodological framework that includes tools like Pubget for article collection and labelbuddy for text annotation. The solid evidence presented for these tools suggests they could streamline the analysis and annotation of scientific literature, potentially benefiting research across a range of biomedical disciplines. While the primary focus is on neuroimaging literature, the applicability of these methods and tools might extend further, offering useful advancements in the practices of meta-research and literature mining.

eLife assessment

This valuable study provides new insight into how non-synaptic interactions affect the activity of adjacent gustatory neurons housed within the same sensillum. The electrophysiological, behavioral, and genetic data supporting the study's conclusions are solid, although the inclusion of additional control experiments would strengthen the study. This work will be of interest to neuroscientists studying chemosensory processing or regulation of neuronal excitability.

eLife assessment

In this important paper, the authors propose a computational model for understanding how the dynamics of neural representations may lead to specific patterns of errors as observed in working memory tasks. The paper provides solid evidence showing how a two-area model of sensory-memory interactions can account for the error patterns reported in orientation estimation tasks with delays. By integrating ideas from efficient coding and attractor networks, the resulting theoretical framework is appealing, and nicely captures some basic patterns of behavior data and the distributed nature of memory representation as reported in prior neurophysiological studies. The paper can be strengthened if (i) further analyses are conducted to deepen our understanding of the circuit mechanisms underlying the behavior effects; (ii) the necessity of the two-area network model is better justified; (iii) the nuanced aspects of the behavior that are not captured by the current model are discussed in more detail.

eLife assessment

This study presents a useful method for using multi-electrode spike recordings to track the time-varying functional connectivity between neurons. However, the evidence is incomplete: a demonstration of the utility of the method relative to conventional approaches is needed. If such a demonstration is made, this could be a tool for gaining insight into circuit structure.

eLife assessment

This important study reports human single-neuron recordings in subcortical structures while participants performed a tactile detection task around the perceptual threshold. The study and the analyses are well conducted and provide solid evidence that the thalamus and the subthalamic nucleus contain neurons whose activity correlates with the task, with stimulus presentation, and even with whether the stimulation is consciously detected or not. The study will be relevant for researchers interested in the role of subcortical structures in tactile perception and the neural correlates of consciousness.

eLife assessment

In this valuable study, the authors examine the role of the cytoskeletal regulatory protein Abba in governing the process of cell genesis in the developing cortex. This study provides insights into the mechanisms of microcephaly, a developmental malformation. The evidence supporting the study was felt to be solid, but the reviewers did note some technical weaknesses that limit the strength of some of the interpretations.

eLife assessment

This is a useful study that identifies circadian changes in the gene expression profile of cultured mouse astrocytes. Mechanistic details linking circadian rhythmicity in HERP, a regulator of calcium signals in the endoplasmic reticulum, to altered phosphorylation of Connexin 43 remain currently incomplete. With improved manuscript clarity and statistical analysis, this work could be of interest to the field of astrocyte and circadian biology.

eLife assessment

The authors report that optogenetic inhibition of hippocampal axon terminals in retrosplenial cortex impairs the performance of a delayed non-match to place task. The significance of findings elucidating the role of hippocampal projections to the retrosplenial cortex in memory and decision-making behaviors is important. However, the strength of evidence for the paper's claims is currently incomplete.

eLife assessment

This important study reports a novel approach to studying cerebellar function based on the idea of selective recruitment using fMRI. It provides convincing evidence for task-dependent gating of neocortical input to the cerebellum during a motor task and a working memory task. The study will be of interest to a broad cognitive neuroscience audience.

eLife assessment

This valuable study provides incomplete evidence that white matter diffusion imaging of the right superior longitudinal fasciculus might help to develop a predictive biomarker of chronic back pain chronicity. The results are based on a discovery-replication approach with different cohorts, but the sample size is limited, and the clinical relevance is overstated. The findings will interest researchers interested in the brain mechanisms of chronic pain and in developing brain-based biomarkers of chronic pain.

eLife assessment

The authors used electrophysiology in brain slices and computer modeling and suggest that layer 2/3 pyramidal neurons of the mouse cortex express functional HCN channels, despite little evidence in the past that they are present. The study is useful at the present time, but results are incomplete because the methods, data, and analyses do not always support the conclusions.

eLife assessment

This valuable work describes a highly complex automated algorithm for analyzing vascular imaging data from two-photon microscopy. This tool has the potential to fill gaps in knowledge of hemodynamic activity across a regional network. The underlying methods and results are still incomplete; the biological application provided has several problems that make many of the scientific claims in the paper questionable and the generalizability of the pipeline needs to be further addressed. We believe these concerns could be addressed.

eLife assessment

This is a valuable study that describes the effects of T. pallidum on neural development by applying single-cell RNA sequencing to an iPSC-derived brain organoid model. The evidence supporting the claims of the authors is solid, although further evidence to understand the differences in infection rates would strengthen the conclusions of the study. In particular, the conclusions would be strengthened by validating infection efficiency as this can impact the interpretation of single-cell sequencing results, and how these metrics affect organoid size as well as comparison with additional infectious agents. Furthermore, additional functional validations of downstream effectors could be insightful.

eLife assessment

This is an important study on changes in newborns' neural abilities to distinguish auditory signals at 37 weeks of gestation. The evidence of change in neural discrimination as a function of gestational age is convincing, but further analysis of the acoustic signals and description of the infants' language environment would strengthen the interpretation of the results. The work contributes to the field of neurodevelopment and suggests potential clinical applications in neurodevelopmental disorders.

eLife assessment

This work presents a potentially important behavioral finding: that perceptual learning may not only improve but also distort the appearance of visual stimuli. The strength of the presented evidence in support of the main claim is however incomplete, and requires further analyses to confirm that perceptual learning does increase overestimation bias, and clarify why a very large baseline overestimation bias is present in the data.