Neuroscience

eLife assessment

This is a potentially valuable study suggesting that neuronal-specific loss of function of the RNA splicing factor Ptbp1 in striatal neurons induces dopaminergic markers and alleviates motor defects in a 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's Disease. If properly replicated, the claims of the manuscript are remarkable and identify a straightforward mechanism with therapeutic relevance for the treatment of motor deficits in Parkinson's Disease. However, while the rescue of motor deficits with Ptbp1 manipulation is solid, the strength of the evidence supporting the induction of a dopaminergic neuronal identity is incomplete. The study nevertheless addresses recent controversial literature on cell reprogramming in Parkinson's Disease and will be of interest to researchers with a focus on the application of gene therapy to rescue neurodegeneration.

eLife assessment

This valuable study provides insights and strategies for assessing laminar structure in vivo in the visual cortex of the macaque monkey with high-density linear electrode arrays. The paper provides solid evidence demonstrating that signals in higher frequency bands, related to the discharge of action potentials, are of substantially better use for achieving well-resolved cortical layer identification than are signals in lower frequency bands typically associated with local field potentials and standard-practice Current Source Density (CSD) analyses. These findings are of interest to electrophysiologists seeking to make comparisons between cortical layers.

eLife assessment

This valuable manuscript sets out to identify sleep/arousal phenotypes in larval zebrafish carrying mutations in Alzheimer's disease (AD)-associated genes. The authors provide detailed phenotypic data for F0 knockouts of each of 7 AD-associated genes and then compare the resulting behavioral fingerprints to those obtained from a large-scale chemical screen to generate new hypotheses about underlying molecular mechanisms. The data presented are solid, although extensive interpretation of pharmacological screen data does not necessarily reflect the limited mechanistic data. Nonetheless, the phenotypic characterization presented is comprehensive, and the authors develop a well-designed behavioral analysis pipeline that will provide considerable value for zebrafish neuroscientists.

eLife assessment

This study addresses an important, understudied question using approaches that link molecular, circuit, and behavioral changes. The findings that Netrin-1 and UNC5c can guide dopaminergic innervation from the nucleus accumbens to the cortex during adolescence are solid. The data showing that the onset of Unc5 expression is sexually dimorphic in mice, and that in Siberian hamsters environmental effects on development are also sexually dimorphic are also solid. Reviewers identified significant gaps in evidence for specificity of Netrin-1 expression, which, if filled, would strengthen the evidence for some of the claims. Future work would also benefit from Unc5C knockdown to corroborate the results and investigation of the cause-effect relationship. This paper will be of interest to those interested in neural development, sex differences, and/or dopamine function.

eLife assessment

van Vliet and colleagues show a correlation between internal states of a convolutional neural network (CNN) trained on visual word stimuli with three specific components of evoked MEG potentials during reading in humans. The findings are useful, but the current results remain incomplete, without evidence that the CNN can produce any of the phenomena that the human visual system is known to have (e.g., feedback connections, sensitivity to word frequency), or that the model has comparable performance to human behaviour (i.e., similar task accuracy with a comparable pattern of mistakes).

eLife assessment

In this valuable study, the authors use a computational model to investigate how recurrent connections influence the firing patterns of grid cells, which are thought to play a role in encoding an animal's position in space. The work suggests that a one-dimensional network architecture may be sufficient to generate the hexagonal firing patterns of grid cells, a possible alternative to attractor models based on recurrent connectivity between grid cells. However, the support for this proposal was incomplete, as some conclusions for how well the model dynamics are necessary to generate features of grid cell organization were not well supported.

eLife assessment

This useful study reports how neuronal activity in the prefrontal cortex maps time intervals during which animals have to wait until reaching a reward and how this mapping is preserved across days. However, the evidence supporting the claims is incomplete as these sequential neuronal patterns do not necessarily represent time but instead may be correlated with stereotypical behavior and restraint from impulsive decision, which would require further controls (e.g. behavioral analysis) to clarify the main message. The study will be of interest to neuroscientists interested in decision making and motor control.

eLife assessment

This study presents a useful exploration of the complex relationship between structure and function in the developing human brain using a large-scale imaging dataset from the Human Connectome Project in Development and gene expression profiles from the Allen Brain Atlas. The evidence supporting the claims of the authors is solid, although the inclusion of more systematic analyses of structural and functional connectivity with respect to myelin measures and oligodendrocyte-related genes, and also more details regarding the imaging analyses, cognitive scores, and design and validation strategies, would have strengthened the paper. The work will be of interest to developmental biologists and neuroscientists seeking to elucidate structure-function relationships in the human brain.

eLife assessment

This study provides a valuable contribution to our understanding of the mechanisms underlying the limited capacity to process rapid sequences of visual stimuli by reporting convincing evidence that the attentional blink affects neurally separable processes of visual detection and discrimination. The motivation for some of the analyses and the connection to previous empirical and theoretical work can be improved. The study will be of interest to neuroscientists and psychologists investigating perception and attention.

eLife assessment

This important study expands our understanding of the role of two axon guidance factors in a specific axon guidance decision. The strength of the study is the compelling axonal labeling and quantification, which allows the authors to establish precise consequences of the loss of each guidance factor or receptor.