Neuroscience

Evaluation Summary:

The authors explored the relationship between amyloid-beta and tau deposition and neural oscillations in Alzheimer's disease (AD) by using a computational neural mass model that can generate neurophysiological power spectra comparable to EEG- or MEG-like, macroscopic brain activity assessments. This analysis demonstrates the different, frequency-specific effects of amyloid-beta and tau proteins on excitation and inhibition, providing an integrated, multimodal explanation of the AD pathogenesis.

(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 measures the strength, timing, feature specificity and for the first time - spatial extent - of pre-saccadic processing of peripheral target information at the fovea, when fixation is not constrained. The authors conclude that saccade preparation causes feature-specific pre-saccadic visual enhancement restricted largely to the center of gaze. The manuscript is based on a rigorously curated dataset, it is well written and illustrated, and will be of potential interest to a broad readership of vision scientists, neuroscientists, and modelers. However, some key weaknesses in the interpretation of data were identified, which call into question the conclusion that the foveal enhancement observed can only be explained in terms of saccade preparation, thus weakening our ability to infer its mechanistic substrates.

(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:

Lupkin and McGinty studied gaze patterns in monkeys during value-based decision-making to determine whether relationships between gaze and choices that have been described in humans are also present in monkeys. Although previous literature has interpreted the effects of gaze on choice behavior to mean that attention to an option influences the decision that is made, a full understanding of the mechanisms underlying these biases will ultimately require data from non-human primates, making this an important and timely study. The authors use a clever task design to show that, as in humans, value-based choices are related to the amount of time spent viewing each option. The study is well-designed and the topic is significant to the field, but reviewers raised concerns about potential confounds and limitations not addressed by the current analyses.

(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 a remarkably ambitious study that has been skilfully executed on a strong number of control participants, amputees, and one-handers. The complementarity of state-of-the-art uni- and multi-variate analyses are in the service of the research question, and the paper is clearly written. The main contribution of this paper, relative to previous studies, resides in the mapping of multiple face-part all at once in the three groups. The study suggests that the deprived hand cortical territory is not invaded by the facial cortical neighbor, the forehead, but instead by the lips that are more distant but functionally related to the hand as it can be used to compensate hand loss for manipulating objects.

(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 name with the authors.)

Evaluation Summary:

This manuscript reveals the contribution of intrinsic excitability to the formation of cortical neuronal ensembles. By combining optogenetic and electrophysiological approaches in vitro, the authors provide new insight regarding the role that plasticity of membrane excitability (intrinsic plasticity) plays in synaptic plasticity and the formation of memories.

(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 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.)