Neuroscience

Evaluation Summary:

This paper uses an impressively rich dataset (obtained and curated by the authors) to compare the structural brain connectomes of many animals spanning 6 taxonomic orders. The approach is innovative and relies on graph theoretical measures to describe the connectivity, which means it can be done without the need to spatially/functionally match the brains. The authors find that there is more variability between than within order. They attribute this effect to changes in local connectivity features, whereas global patterns are preserved. The approach can potentially be a useful way to study phylogeny and brain evolution.

(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 name with the authors.)

Evaluation Summary:

This paper presents an exciting new automated package to investigate the hippocampal organization in new ways. As such, this package will be equally interesting for the fundamental basic and clinical neurosciences.

(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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript will be of interest to scientists working on learning and memory and synaptic plasticity. It provides a useful overview of different forms of plasticity taking place in the learning and memory center of the fly, the mushroom body. The study mostly uses an acetylcholine sensor to image activity, which is novel and helps to tie together previous studies reporting memory-induced changes in calcium transients. In particular, the study highlights the compartmentalised plasticity along Kenyon cell axon terminals, the main cell type of the mushroom body. The current version of the manuscript could be improved by including some key issues: (1) behavioral experiments for the Cac knock-down experiments, (2) specific controls for some of the imaging experiments, (3) consideration of the role of dopaminergic neurons and (4) acknowledgment of the complexity of the mushroom body circuit and the literature that has addressed this previously.

(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 examined how mixture odors are represented in the mouse olfactory bulb. The authors found that compared to the responses in anesthetized mice, mixture responses are more linear in awake mice regardless whether the mice were engaged in a behavioral task or not. The results are potentially important as the results differ from previous studies which were done mostly in anesthetized animals, but the reviewers raised concerns for the validity and the strength of the 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 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript will be of interest to readers in the field of anatomy and hippocampal physiology. The authors provide characterization of a novel projection pathway from layer 5a neurons in the MEC to CA1 of the hippocampus. They utilize cell specific viral labelling techniques, RNA-sequencing based projection mapping, and optogenetic aided in vitro physiology. The anatomical conclusions are well supported by the data. Future functional experiments will be necessary to establish the functional role of the projection.

(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 manuscript suggests that the neuronal circuit from the basal amygdala (BA) to the ventral hippocampus (VH) consists of both excitatory and inhibitory projections to specific targeted areas. The main message is that excitatory input specifically targets VH neurons that in turn project to the BA and nucleus accumbens (NA). In contrast, BA inhibitory input preferentially targets VH neurons that project to the BA to gate place-value associations. The reviewers agree that the manuscript reports potentially interesting data. However, they all agree that the claim made is preliminary and only partially sustained by the submitted experimental evidence.

(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:

The study of cortical regulation of behavior under conflict is novel, timely, and important. It is of broad interest to neuroscientists studying the neural substrates of fear and reward and offers a novel behavioural perspective showing how these opposing motivational states interact to influence behaviour differentially across individuals and how this is regulated by glutamatergic and GABAergic neurons in the prefrontal cortex. The paper uses a variety of cutting-edge tools to dissect the microcircuits of the prefrontal cortex. The claims are generally supported by the data, but some claims comparing individual differences require additional statistical analyses and consideration of potential alternative interpretations for the behavioral phenotypes observed.

(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 #2 agreed to share their name with the authors.)

Evaluation Summary:

The authors develop a new technique allowing simultaneous imaging of hippocampal subfields in behaving mice. This paper will be of interest to the large number of neuroscientists who study the hippocampal circuit, and more broadly to those interested in methods to enable high-resolution in vivo imaging across depths in the brain.

(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 #2 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This study is of broad interest to neuroscientists interested in membrane excitability and translational biologists and physicians eager for robust animal models for disorders involving mutations in the KCNMA gene, such as paroxysmal nonkinesigenic dyskinesia PNKD3. Here, phenotypes of mouse models of three of the more common patient disease-related mutations in KCNMA are evaluated for similarities to patient phenotypes. This work establishes that BK channel mutations linked to human neurological disease can, on their own, cause similar pathology in mice, and it also begins to provide neurological bases for the associated behavioral deficits. Importantly, one of the mutant alleles expressed in mice most closely phenocopies the patient phenotype and will serve as an important animal model for studies seeking therapeutic treatments for the resulting debilitating disease moving forward.

(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 undertake a detailed investigation focused on how the abundance of the sole Cav2 Ca2+ channel Cac in Drosophila is regulated at active zones (AZs) using the larval neuromuscular junction (NMJ) as a model system. The larval NMJ is a particularly powerful system to address this question, and the authors have taken full advantage of the unique approaches available. This work makes important advances in our understanding of AZ Ca2+ channel regulation during development and will be of significant interest to the field.

(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 #2 and Reviewer #3 agreed to share their name with the authors.)