Neuroscience

Evaluation Summary:

The authors developed a set of synthetic proteins, Designed Ankyrin Repeat Proteins (DARPins), that bind gephyrin, the main scaffold protein at inhibitory postsynaptic sites, and characterize them extensively to study gephyrin cluster morphology and biochemistry. In several aspects, DARPins outperform traditional antibodies. This study is clear, well organized and well written, demonstrating that DARPins can be important tools synaptic, cellular and circuit neuroscience 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. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

The present manuscript examines cortical representations of basic visual attributes following a manipulation shown to enhance plasticity in the adult brain: binocular dark exposure for several days, followed by light re-introduction. The work has fundamental therapeutic and conceptual implications, and will be of potential interest to a broad readership of vision scientists, neuroscientists, clinicians and modelers. The paper is well-written and based on sophisticated experiments. The evidence provided convincingly supports the authors' contention that dark exposure does not have a negative impact on visual representations in V1. The study uses a generally appropriate study design. However, it would benefit from the addition of some key experimental details, and additional analyses and statistical tests to explore alternative interpretations of results.

(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 addresses the toxicity of fluorescent calcium indicators, comparing two series of indicators (GCaMPs and GCaMP-Xs) in mouse neurons. The paper documents GCaMP toxicity during development and following prolonged strong expression, and establishes that GCaMP-X indicators are less toxic. The paper will be of interest primarily to neuroscientists who use fluorescence calcium indicators to monitor calcium dynamics during neuronal development.

(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 is an important study that investigates whether older adults have selective impairments in allocentric navigation (using distal cues to navigate). Using a combination of ecologically inspired real-world navigation, virtual reality, eye tracking, and body-tracking, the study reports, for the first time, that older adults show no difference from younger adults when using geometry to navigate a Y maze. Instead, their deficits appear to relate to perceptual difficulties with processing individual landmarks. This large sample study therefore provides somewhat compelling evidence of age-related difficulties in processing landmarks visually rather than a selective deficit in allocentric navigation.

(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:

A new and interesting operant conditioning paradigm is established for the Drosophila larva. A novel role for serotonergic pathways in the VNC in operant learning points to new circuits and mechanisms for learning and memory. Impressive technology opens doors for new and exciting studies on learned behavior in the small and tractable circuits of the larva.

(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 well-written report provides new insights for neuroscientists studying sleep architecture and stress sensitivity. A particularly important conclusion is that differences in sleep architecture before chronic social defeat stress may serve as a predictive biomarker of stress resilience. Overall the work is very strong, but there are some conceptual and methodological issues that need to be addressed.

(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 will be of interest to the neuroscience community studying brain oscillations. It presents a new method to detect sharp-wave ripples in the hippocampus with deep learning techniques, instead of the more traditional signal processing approach. The overall detection performance improves and this technique may help identify and characterize previously undetected physiological events.

(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:

The experiments presented in this extensive study by Ronzano et al. are a tour-de-force investigating the spatial organization of premotor interneurons in the mouse spinal cord to re-examine the fundamental question of whether there is spatial segregation of interneurons with monosynaptic connections to motoneurons innervating functionally antagonistic (flexor and extensor) pairs of limb muscles. The authors' premotor circuit mapping experiments, involving four different collaborating laboratories applying an extensive set of complementary rabies virus-based trans-synaptic circuit tracing techniques, convincingly demonstrate complete spatial overlap among flexor and extensor premotor interneurons, contradicting previous mapping results that suggest spatial segregation. The present results revise our understanding of the spatial organization of spinal premotor circuits with fundamental implications for understanding spinal motor circuit 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.)

Evaluation Summary:

There is currently a lack of available fine-grained infant-dedicated cortical parcellation maps. The present study fills an important gap in the research of infant brain development by generating an age-dependent functional brain parcellation from birth to 24 months, leveraging on the 1064 high-resolution longitudinal resting-state fMRI scans from 197 infants. These age-specific parcellation maps have the potential to facilitate scientific discoveries, comparisons, and validations in brain functional development. Moreover, the proposed method of establishing functional correspondences across individuals using functional gradient densities can also be applied to study brain changes across lifespan.

(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 name with the authors.)

Evaluation Summary:

This paper will be of interest to neurophysiologists and system neuroscientists interested in memory and more specifically in hippocampo-cortical interactions. Using a combination of imaging and electrophysiological techniques, the study characterizes neocortical activity patterns around awake hippocampal ripples. Unlike sleep ripples, cortical activity seems to be dominated by inhibition around ripples but differences between intrinsic activity and synaptic transmission highlight complex interactions in the underlying neuronal circuits and dynamics.

(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.)