Neuroscience

Evaluation Summary:

Bice et al. present new work using an optogenetics-based stimulation to test how this affects stroke recovery in mice. Namely, can they determine if contralateral stimulation of S1 would enhance or hinder recovery after a stroke? They found that stimulation of the cortex contralateral to the site of stroke impairs recovery from this stroke, and impairs the brain mapping and the connectivity that normally emerges in recovery from stroke. This unexpected finding in a mouse model relates to clinical literature on the role of the contralateral cortex in recovery.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The manuscript introduces a new tool - BigBrainWarp - which consolidates several of the tools used to analyse BigBrain into a single, easy to use and well documented tool. The BigBrain project produced the first open, high-resolution cell-scale histological atlas of a whole human brain. The tool presented here should make it easy for any researcher to use the wealth of information available in the BigBrain for the annotation of their own neuroimaging data. This is an important resource, with diverse tutorials demonstrating broad application.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

Previous studies have indicated that neurons in different cortical areas have different intrinsic timescales. In this study, Pinto and colleagues aimed at establishing the functional significance of intrinsic timescales across cortical regions by performing optogenetic silencing of cortical areas in an evidence accumulation task in mice. The results are of broad interest, but the reviewers identified a few important issues that need to be addressed to validate the authors' conclusions.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This paper addresses researchers interested in architecture and function of the insect central complex as it represents the first comprehensive projectome dataset of any central complex outside Drosophila. The authors use the bumblebee as representative for hymenopterans with their navigation skills. Further, they mine their data for conserved and diverged aspects compared to fly (Drosophila) knowledge and hypothesize how the differences may relate to diverged neural circuit function. Hence, they provide an excellent and comprehensive descriptive resource providing a point of reference for others and a starting point for comparative studies of neural circuits. In particular, this study is the first comprehensive description of columnar neurons in the bumblebee central complex, described through the lens of the recently published fruit fly connectome of the same, homologous neuropil. The comparative approach used here holds promise for describing neural circuits in bees and flies in shared frame of reference. The authors use an approach that reflects a compromise between quick collection of electron microscopy (EM) data and being able to fully reconstruct all neurons in the bumble bee's central complex. The authors are transparent about the method's limitations and draw appropriate conclusions.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

In this rigorously conducted meta-analytic study, the authors investigated the functional and structural abnormalities associated with developmental dyslexia across languages. Convergent and divergent functional and structural changes as well as language-universal and language-specific brain alternations related to dyslexia are found. In general, the study has generated important results and the findings are of interest to readers in educational psychology/neuroscience fields, especially those focusing on reading development and dyslexia. The analytic approach used in this study is cutting-edge, the data support the main claims, and a detailed discussion is presented.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

The authors perform a tour-de-force study of classical conditioning in fly larvae. Experiments are original, findings are exciting, and we expect this paper to have a substantial impact. There is potentially an issue in the assay of larvae preference taking an hour of unrewarded presentation of CO2, while the training and extinction happen on much shorter scales, muddying the ability to interpret the results. A mathematical model of the conditioning process is also missing, which also makes interpretation harder.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This study uses the approach of labeling neurons with distinct birthdates so they can be differentiated in experiments performed later in development. The authors then test morphological, functional and circuit inputs/outputs patterns of these neurons by using immunohistochemistry, slice electrophysiology, retrograde labelling, morphological reconstructions and behavioral assays. The manuscript is likely to make a strong impact in the field of developmental neuroscience and a good impact related to more general cellular and molecular neuroscience.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This study reports that calsyntenin-3, a synaptic adhesion molecule, is expressed in cerebellar Purkinje cells and that acute knockout of calsyntenin-3 increases excitatory synapse density and decreases inhibitory synapse density. The manuscript provides compelling evidence that elimination of calsyntenin-3 from cells in the cerebellar cortex alters the E/I balance for Purkinje cells by increasing the strength of excitatory parallel fiber inputs and decreasing the strength of inhibitory inputs. However, it would have been far better to selectively target Purkinje cells, but that was not done. This is the first study showing that a particular synaptic adhesion molecule regulates excitatory and inhibitory synapse in opposite directions.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The authors present the first digital adult zebrafish brain anatomy atlas that includes ten highly informative markers for different brain regions and cell types. The authors utilize new clearing techniques to enable staining of the whole fixed zebrafish adult brains, and light sheet microscopy fluorescent imaging to obtain high resolution three-dimensional data. Several individual dataset for each marker are registered and aligned to an anatomical model using fluorescent cell nuclei and autofluorescence patterns by state of the art volume registration algorithms. The results appear to be of high quality. The authors also provide a detailed and state-of-the-art anatomical annotation of brain regions. Using ten different antibodies to fluorescently label different neuron types, stem cells and glia, proliferation zones, and some specific anatomical regions, the authors demonstrate the utility of their database. This will be a valuable resource for neurobiology research in zebrafish.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This study will be of interest to scientists involved in high-level vision. The data provide a compelling demonstration of the causal role of three key visual areas in context-based object recognition. The key claims of the manuscript are supported by the data, and are strengthened by the pre-registration of each of the three experiments.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their names with the authors.)