Neuroscience

eLife Assessment

This study describes a highly complex automated algorithm for analyzing vascular imaging data from two-photon microscopy. The proposed tool has the potential to be extremely valuable to the field and to fill gaps in knowledge of hemodynamic activity across a regional network. The biological application provided, however, has several problems that make many of the scientific claims in the paper incomplete.

eLife Assessment

This important study enhances our understanding of ephaptic interactions by utilizing earthworm recordings to refine a general model and use it to predict ephaptic influences across various synaptic configurations. The integration of experimental evidence, a robust mathematical framework and computer simulations convincingly demonstrate the effects of action potential propagation and collision properties on nearby membranes. The study will interest both computational neuroscientists and physiologists.

eLife Assessment

In this important manuscript, Ryan et al perform a genome-wide CRISPR based screen to identify genes that modulate TDP-43 levels in neurons. They identify a number of genes and pathways and highlight the BORC complex, which is required for anterograde lysosome transport as one such regulator of TDP-43 protein levels. Overall, this is a convincing study, which opens the door for additional future investigations on the regulation of TDP-43.

eLife Assessment

This valuable study uses high-field fMRI to test the hypothesized involvement of subcortical structures, particularly the striatum, in updating working memory. The study overcomes limitations of prior work by applying high-field imaging with a more precise definition of regions of interest in the brain. Thus, the empirical observations are of use to specialists interested in working memory gating or the reference back task specifically. The evidence is generally solid, but strong conclusions on dopaminergic contributions must await additional work using molecular imaging or related techniques.

eLife Assessment

This important study successfully applies an innovative chemogenetic tool to investigate cerebellar function to advance our understanding of the contributions of Purkinje cell populations to postural control in larval zebrafish. The evidence supporting the conclusions is convincing and supported by rigorous statistical analysis. The study highlights the power of combining genetically targeted perturbations with quantitative high-throughput behavioral analysis and original microscopy tools.

eLife Assessment

This important study provides convincing evidence that developing neurons in the neocortex regulate glial cell development. The data demonstrates that the transcription factor FOXG1 negatively regulates gliogenesis by controlling the expression of a member of the FGF ligand family and by suppressing the receptor for this ligand in developing neurons. This study leads to a new understanding of the cascade of events regulating the timing of glial development in the neocortex.

eLife Assessment

This important study introduces a new cortical circuit model for predictive processing. Simulations effectively illustrate that, with appropriate synaptic plasticity, a canonical layer 2/3 cortical circuit - comprising two classes of interneurons providing subtractive and divisive inhibition - can generate uncertainty-modulated prediction errors by pyramidal neurons. The model is compelling; although it relies on many assumptions and has not yet been compared directly to data, the model does align with empirical observations and yields a range of testable predictions. The study is expected to be of great interest to those involved in cortical and predictive processing research.

eLife Assessment

This valuable study reports the induction of supernumerary inner hair cells in the mouse cochlea upon reducing the expression level of a tight-junction protein (claudin-9) at developmental stages. Although these ectopic hair cells are functional and persists through adulthood, the evidence supporting some of the claims is incomplete, particularly regarding the underlying mechanisms of cell differentiation and the potential of the approach for hair-cell regeneration. The work will be of interest to scientists working in the development and regeneration of hair cells in the inner ear.

eLife Assessment

What makes one member of the species behave differently from another? This is a core problem in behavioral neuroscience. This valuable study seeks an answer for the specific case of the fruit fly expressing preferences for one odor over another. By a combination of behavioral measurements, neurophysiology, and network modeling, the authors find solid evidence for at least one locus of individuality in the peripheral olfactory system.

eLife Assessment

This study tested the specific hypothesis that age-related changes to hearing involve a partial loss of synapse connections between sensory cells in the ear and the nerve fibers that carry information about sounds to the brain, and that this interferes with the ability to discriminate rapid temporal fluctuations in sounds. Physiological, behavioral, and histological analyses provide a powerful combination to test this hypothesis in gerbils. Contrary to previous suggestions, it was found that chemically-induced isolated synaptopathy (at similar levels as observed in aged gerbils) did not result in worse performance on a behavioral task measuring sensitivity to fine-structure. Further, altered neural coding of rapid fluctuations produced no perceptual deficits in either these gerbils or in aged gerbils. These findings are important for understanding age-related changes to hearing; however, the evidence provided is incomplete due to problems in interpretation and the discussion of possible confounds and/or limitations of these data that currently limits mechanistic insight.