Neuroscience

Evaluation Summary:

This is an interesting paper that tries to quantify brain asymmetry in connectivity, looks at the heritability of this asymmetry, and compares it between humans and monkeys. The approach taken here is to first project the connectivity information into a low dimensional sub-space and then to quantify brain asymmetry in this low dimensional representation. The benefit of this approach is that it simplifies the problem to looking at scalar indices rather than matrices, and that it allows comparisons between subjects and species in connectivity space. This work should be of interest to the field of brain asymmetry and evolution. However, there are fundamental issues with the method, as outlined in the review. The paper would also benefit from a stronger focus on the biological interpretation. At present, the main contribution of this work is providing interesting data.

(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 manuscript by Kim et al. validates the previously generated Tcf4 LGSL mouse model (developed by the authors' group; Kim et al. 2020) for Pitt-Hopkins syndrome (PHS) by normalizing the Tcf4 expression level. They found that reinstating Tcf4 expression improves a subset of behavioral abnormalities, including anxiety-like behavior, activity level, innate behaviors and memory. Moreover, neonatal ICV injection of Cre mediating restoration of gene expression also improved the behavioral abnormalities and altered LFP spectra, and partially recovered the expression level of downstream target genes for Tcf4. This provides a proof-of-concept for therapeutic interventions against PHS. The writing and data quality are excellent, and clear limitations of current study are well described. However, there are some areas for further improvement.

(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, one of the largest of its kind, replicate previous findings regarding impairment of sleep rhythms in patients with schizophrenia relative to healthy controls. Specifically, slow but not fast sleep spindles are correlated with the severity of the symptoms.

(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:

In this report, the authors have combined analysis of the Connectivity Map with small molecule screens in zebrafish to identify compounds that may spare ototoxicity induced from cisplatin. This is an important limitation of this effective and widely used chemotherapeutic agent and has the potential to create approaches to limit the neurotoxicity induced by cisplatin.

(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 use C. elegans to explore the relationship between shank (an Autism-associated gene orthologue), CaV1 (Ca) channels, and BK (slo) calcium-dependent K channels in controlling muscle excitability. The data annotate a novel activity of Shank as an organizer of ion channel domains with potential relevance to human disease.

(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:

Bräcklein et al. provide compelling data suggesting that humans cannot learn to independently control multiple motor units innervating a single lower-limb muscle. These results suggest that common drive to motor units, along with the classical size-recruitment order, will impose strong constraints on the use of high-resolution muscle recordings for controlling brain-computer interfaces. Additional analysis related to task construction and motor unit identification/sorting is required to justify this claim.

(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 is an interesting article studying human color perception using MEG. The specific aim was to study differences in color perception related to different S-, M-, and L-cone excitation levels and especially whether red color is perceived differentially to other colors. The study addresses an interesting question. The methods are strong. The data broadly support the conclusion, although some additional analyses would offer further support.

(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 manuscript by Nagaraja et al. examines the synapse-specificity of alpha-synuclein aggregation and corresponding circuit dysfunction in the amygdala. Using confocal microscopy and slice electrophysiology, along with alpha-synuclein knockout mice and preformed fibrils, the authors demonstrate that cortico-amygdala, but not thalamo-amygdala, inputs are more vulnerable to alpha-synuclein aggregation and corresponding synaptic dysfunction. This has important implications for the etiology of psychiatric deficits that are common in Parkinson's disease.

(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 question addressed in this manuscript is of potential interest for neurodevelopmental biologists studying the role of molecular factors released from thalamocortical axons in the establishment of cortical layers. The work clarifies the contribution of distinct thalamic secretory proteins in cortical development. Overall, although the data are properly controlled and analyzed, there are several aspects of the manuscript that need to be addressed and improved to support the conclusions raised by the authors.

(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 study investigates the mechanisms by which distributed systems control rhythmic movements of different speeds. The authors train an artificial recurrent neural network to produce the muscle activity patterns that monkeys generate when performing an arm cycling task at different speeds. The dominant patterns in the neural network do not directly reflect muscle activity and these dominant patterns do a better job than muscle activity at capturing key features of neural activity recorded from the monkey motor cortex in the same task. The manuscript is easy to read and the data and modelling are intriguing and well done. Further work should better explain some of the neural network assumptions and how these assumptions relate to the treatment of the empirical data and its interpretation.

(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.)