Neuroscience

Evaluation Summary:

This paper will be of broad interest to readers in the field of motion perception. The authors use concurrent psychophysics and single unit recordings, along with modeling, to investigate how primate cortical area MT uses specific visual signals to make inferences that distinguish between visual motion induced by self-motion and the motion of other objects in the world. The experiments and stimuli are expertly designed and the analyses are careful.

(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:

Exocytosis of synaptic vesicles is mediated by synaptic SNARE proteins that overcome the energy barrier for membrane fusion by assembling into a helical bundle, thus pulling the membranes together. Here the authors have introduced mutations into the membrane-proximal region and transmembrane domain of one of the SNAREs (syntaxin 1a) showing that not only charge reversal but also palmitoylation of the transmembrane domain influence both spontaneous and evoked neurotransmitter release. The results add important details to our understanding of the late steps in SNARE-mediated exocytosis.

(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 manuscript is of particular interest to researchers in the fields of neuroecology of insect olfaction and of insect-plant interactions in general. The authors investigate the olfactory signals that guide the specialist hawkmoth Manduca sexta towards plants that are used for oviposition and for nectar-feeding in a natural setting. How insects distinguish useful information from irrelevant information is an important question. The authors use elegant chemical ecology techniques and recordings of neuronal activity to ask how female moths (Manduca sexta) could discriminate co-occurring behaviorally relevant vs irrelevant plant and floral volatiles.

(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 paper presents a tour de force examination of the role of PAG CCK neurons in threat. It is exemplary in the use of a variety of high and low threat tasks along with corresponding behavioural measures, as well as gain and loss of CCK function approaches. The results reported will be of significant benefit for those studying the behavioural and neural mechanisms of learned and unlearned threat, and decision-making in threatening situations.

(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 a very exciting study that presents a novel approach to examining dopamine release with spatial precision that is so far unrivaled. This manuscript is also important and timely in the field of biosensor development and of potential interest to neuroscientists who study neurochemical release. It introduces a synthetic nanofilm with high spatiotemporal resolution and quantal sensitivity to dopamine measurement. By utilizing this technology to visualize sub-cellular dopamine efflux, the work provides new insights into the spatiotemporal dynamics and protein machinery of somatodendritic dopamine release. The authors identify hotspots for DA release and also provide evidence for DA release in the presence of TTX, suggesting the occurrence of quantal release.

(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:

In the present manuscript by Blake et al., the investigators show that myocardial infarction (MI) leads to increased sulfation of CSPGs in the cardiac scar. The investigators subsequently demonstrate that reducing sulfation with a sulfatase, arylsulfatase B (ARSB), promotes sympathetic neurite growth in vitro and ex vivo in a co-culture system. This paper provides interesting results regarding neural remodeling of the heart and has implications for visceral innervation in health and disease. This work is important in highlighting the role of neural-myocardial interactions after MI and offering a potential pathway to target in preventing post-MI sudden cardiac death.

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

Evaluation Summary:

This study investigates oculomotor behavior of cortically-blind patients (with lesions in area V1) performing a saccade and ocular following response toward a cued moving target placed either in their intact or in their blind visual field. Whereas perceptual training led to a good recovery of perceptual performance in the blind field, the ocular following response did not appear to benefit from this training. The authors conclude that V1 lesions result in impaired transmission of signals selectively driving the ocular following response. The manuscript is based on a valuable patient dataset, well written and illustrated, and will be of potential interest to a broad readership of vision scientists, neuroscientists, and clinical neurologists. However, some major weaknesses in the analysis and interpretation of data call into question the conclusion that the selective eye movement deficit reveals a true perception-action dissociation.

(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 is of potential interest to psychologists and cognitive neuroscientists studying learning, decision-making, belief formation and metacognition. The authors use a clever, elegant task in which people make decisions with or without control over the information they sample, and link the cognitive processes at play to MEG and pupillometry signatures. The key finding is that when participants have control over information sampling (i.e. are seeking information), they need more contradictory evidence in order to switch their choices, and such switches are made with lower confidence. Anticipatory suppression of alpha-band activity in occipital and frontal regions occurred prior to decision switches, while pupil dilation increased post-switch. The authors propose a computational model to account for behavioral differences between conditions. However, some of the conclusions may not be fully supported by the data and alternative interpretations are possible; therefore further analyses are required to bolster the authors' 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This study is of great interest to a broad group of neuroscientists including those studying plasticity in the nervous system and in neurodevelopmental disorders such as autism. The current work illustrates the importance of protein phosphorylation in regulating a form of homeostatic plasticity known as synaptic scaling, which has been associated with different neurodevelopmental disorders. In particular, the authors provide compelling evidence that the phosphorylation state of one synaptic scaffolding protein, Shank 3, is a necessary part of a complex signaling pathway mediating synaptic scaling and thus could be therapeutically useful for certain associated disorders.

(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 uses both humans and rats to demonstrate that the level of glutathione in the nucleus accumbens correlates with effortful behaviors. The authors provide causal evidence for glutathione in rats by manipulating enzymes involved in the synthesis of glutathione. Although how exactly glutathione regulates effort-related behavior remains to be clarified, overall, the study gives convincing evidence for an important role of glutathione in nucleus accumbens in regulating the willingness to invest effort to obtain reward or escape an aversive situation.

(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.)