Neuroscience

Evaluation Summary:

In their manuscript, Eira et al. investigate the role of transthyretin in promoting axon elongation by modulating microtubule dynamics. The data point to a possible role of transthyretin in regulating microtubule dynamics by modulating tubulin acetylation levels during axon outgrowth. With additional support to strengthen this conclusion, the paper will be of interest to those in the neurodevelopment, neurodegeneration, and microtubule cytoskeleton fields.

(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 behavioural study in healthy participants examines how people trade-off a brief phasic pain stimulus with a monetary reward, reporting a quadratic effect of pain on decision making. It supports and adds to previous findings of a context-dependency deriving from the distribution of rewards, which is a deviation from conventional rational choice theory (which proposes that a particular level of pain should carry the same price, regardless of small context changes). Broadly, the reviewers found the work well executed and the data compelling, but there were some suggestions for alternative explanations that are not ruled out given the current 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:

Menicucci et al. investigate the implication of sleep in the maintenance of ocular dominance plasticity in adult humans. This is an interesting study as it shows that sleep can maintain the changes in ocular dominance obtained after applying an eye-path on the dominant eye for two hours. This contrasts with the rapid decline of these changes during quiet wake in darkness. The authors further report correlations between sleep oscillations and the magnitude of the plasticity effect. These results highlight a possible implication of sleep in a new form of plasticity

(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 study, the role of different cortical areas on three distinct tasks all relying on the same virtual maze set-up was examined using optogenetic interventions and calcium imaging. The paper is potentially of interest to people interested in understanding the neural substrates of learning and how these can be impacted by previous knowledge and experience of stimuli. It could also be of use to behavioral neuroscientists when considering possible order effects of 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 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript probes the mechanism of postsynaptic retinoic acid (RA) signaling on presynaptic function. BDNF has important roles in synaptic plasticity, but how retrograde BDNF signaling is controlled following synaptic inactivity is unclear. The authors use genetic tools to localize the action of different components of the pathway to pre- or post-synaptic compartments and use biochemical approaches to define a molecular link between retinoic acid and local translation of distinct BDNF transcripts. The findings presented here fill a gap in our knowledge regarding how presynaptic function is adaptively modulated by BDNF by highlighting the role of RA in this process. The experiments have been well-executed and the data provide compelling support for the model proposed 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 #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

The authors report on the coordination mechanisms between oscillations recorded in the CA1 subfield of the hippocampus, prefrontal cortex, and olfactory bulb and cell ensemble activity in CA1 and prefrontal cortex that are associated with odor-cued decision making. The findings support the hypothesis that the beta rhythm plays a role in coordinating CA1-prefrontal cortex ensembles associated with an animal's accurate decisions. Sensory-guided decision-making is of broad significance to many readers who are studying executive functions and cognitive behaviors, and the observations reported in this manuscript provide insights into mechanisms that may support these functions and behaviors.

(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:

Houy and co-workers investigated the function of Munc13-1 and ubMunc13-2 in chromaffin cells and the interaction with phorbol esters (PMA). They combined calcium uncaging, capacitance measurements, amperometry, and activity-dependent movements of the EGFP-labeled Munc13 proteins. This study reveals that phorbolesters have a stimulatory effect via ubMunc13-2 but an inhibitory effect via Munc13-1. These opposing effects of the two Munc13 paralogs are surprising considering the closely related domain architectures.

(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 manuscript, the authors specifically look at the interaction between epidural stimulation of the spinal cord and the descending input evoked voluntarily in 2 intact monkeys. The results show that spinal stimulation could facilitate or suppress voluntarily evoked EMG and wrist torque, depending on voluntarily evoked activity as well as the stimulation parameters. This shows that spinal stimulation could enhance the descending inputs in cases of partial lesions. The conclusions of this paper are well supported by data, although they could be made stronger with additional analysis and clarification.

(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 by Fox, Birman, and Gardner combines human behavioral experiments with spatial attention manipulation and computational modeling (image-computable convolutional neural network models) to investigate the computational mechanisms that may underlie improvements in behavioral performance when deploying spatial attention. Through carefully controlled manipulations of computational architecture and parameters, the authors dissociate the effects of different tuning properties (e.g. tuning gain vs. tuning shifts) and conclude that increases in gain are the primary means by which attention improves behavioral performance. The analyses and results are technically sound and clearly presented, but the generality of the conclusions is limited by certain modeling/task choices made in the work.

(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 paper analyses the synaptic connections of two subsets of clock neurons in the Drosophila brain, the small ventral lateral neurons and the dorsal lateral neurons that control the sleep-wake behavior. The study reveals interesting features of the clock network, including the high heterogeneity of the LNd subset and the existence of non-clock cells that are predicted to act as "inter-clock neurons". The manuscript will be of interest to chronobiologists and neuroscientists working on neuronal networks, and it provides new insights into circadian clock network organization that may be of general value. The data analysis is rigorous, and the conclusions are justified by the 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.)