Neuroscience

Evaluation Summary:

Given the well-known importance of the SYNGAP1 mutations in the pathophysiology of neurodevelopmental disorders and the key regulatory roles of SynGAP1 for excitatory synaptic functions, this study provides timely and comprehensive sets of data supporting the in vivo functions of individual SynGAP1 splice variants, including the alpha-1/2 variants, and suggests the therapeutic potential of increasing specific SynGAP1-alpha variants.

(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 is an interesting quantitative study of the anatomical connections of a region of prefrontal cortex that has often been overlooked - the Ventrolateral Prefrontal Cortex. The idea that this is a special region that is different to both the rest of ventrolateral prefrontal cortex and probably the rest of orbitofrontal cortex is important because it helps us understand some otherwise puzzling results. The quantitative analysis of connections is an unusual strength of the study as is the comparison of tracer data in macaques, fMRI connectivity data in macaques, and human fMRI connectivity 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 paper employs sophisticated modeling of human behavior in well-controlled tasks to study how limitations of working memory constrain decision-making. Because both are key cognitive processes, that have so far largely been studied in isolation, the paper should be of broad interest to neuroscientists and psychologists. The observed working memory limitations support and extend previous findings, but some of the most interesting claims need additional 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:

Soyman and colleagues investigate intensity coding for the "pain of others" in the human insula with intracranial human recordings. Additional data of a related fMRI study is analyzed and discussed in the context of the intracranial data. The paper addresses an important research question of broad interest, with extremely unusual data which is investigated in considerable detail.

(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:

Morozova et al. describe potential mechanisms contributing to the flexibility of burst patterns and dynamic responses to perturbations within an isolated reciprocally inhibitory circuit derived from the stomatogastric ganglion of the crab. The authors use the dynamic clamp approach to study the interactions between pharmacologically isolated, intrinsically silent gastric mill neurons, an approach pioneered by Andrew Sharp in the 1990s. The authors demonstrate that the mechanisms of switching between components of the reciprocally organized half-center network are not fixed and may shift to favor a release or escape mechanism depending on factors such as the synaptic threshold, Ih conductance, and synaptic conductance. This is a fundamentally important study because reciprocally organized networks are ubiquitous and found virtually in every organism. It is assumed that this half-center-type network organization governs rhythmic activity with a wide range of functions.

(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. Reviewers #1, #2 and #3 agreed to share their names with the authors.)

Evaluation Summary:

This is an interesting study of the relation between vividness of visual imagery and the pupillary light response that can result from it. It provides evidence for the absence of imagery in individuals that self-report as aphantasic. The results will likely be of interest to researchers in a range of disciplines such as psychology, neuroscience and philosophy. There were some shared concerns related to demand characteristics and eye movements, and the authors might be able to address these concerns with more data analysis and/or control 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 #2 agreed to share their names with the authors.”)

Evaluation Summary:

This study investigates and characterizes the representations of actions in naturalistic movie stimuli. The combination of the analytical techniques and stimulus domain make the paper likely to be of broad interest to scientists interested in action representation amidst complex sequences. This paper will potentially broaden our understanding of visual action representation and the extraction of such information in natural settings, but clarification of the analyses and aspects of the data are required to strengthen the claims.

(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 covers a series of experiments designed to characterize conditioned pain processing using a novel animal model in which mechanical nociception (von Frey test) is assessed following exposure to contextual cues that have been paired with visceral pain (intraperitoneal acid injection). These experiments address an important topic from a translational perspective, both because learning is an important but understudied contributor to the human pain experience and because there is evidence for sex differences in human pain expression. The results reveal that such cues exert complex, dose- and sex-dependent effects on pain processing that will be of broad interest to researchers across fields of associative learning, neuroscience, and pain research.

(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:

The manuscript by Zhang et al. describes the combined use of a new surgical procedure and therapeutic hypothermia to deliver local therapy to the optic nerve in large mammals. In addition, the work describes a novel computer program that can optimize surgical approaches to access the optic nerve endonasally by using anatomical parameters obtained by tomography scan. The study represents a significant step forward in the use of therapeutic hypothermia in the treatment of ocular conditions and is of interest to neurobiologists studying therapeutic interventions for acute trauma to the optic nerves or to other regions of the central nervous system.

(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 study addressed interactions between two key striatal transmitters, dopamine and acetylcholine during an appetitive behavioral task. Helping to reconcile conflicting evidence in the literature, the data show that changes in both transmitters are correlated and that decreases in acetylcholine with reward and reward cues is only partially a consequence of elevated dopamine release acting at D2 dopamine receptors on striatal cholinergic interneurons. The behavioral significance of this correlation remains to be fully clarified. This manuscript will be of interest to those interested in the neural correlates of appetitive behavior and dopamine and striatal function.

(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.)