Neuroscience

Evaluation Summary:

The authors find that long-range interhemispheric synapses are selectively weakened following loss of function of the gene mediating fragile X syndrome, the most common inherited form of intellectual disability. Using clever genetic and physiological approaches in mice, the authors show that the effect is cell autonomous and occurs postnatally by impeding the normal developmental strengthening of these synapses. The results convincingly enhance our understanding of the complex pathophysiology of neurological dysfunction in this developmental disorder.

(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 uses non-invasive imaging to look at the coupling within and between layers and regions of the human visual cortex during the modulation of attention. The results presented here are a re-analysis of a previously recorded dataset, but the novelty is the analytic technique used to relate laminar connectivity to rhythms. This in principle promises to advance the field of both oscillations and laminar fMRI and could deliver valuable insights. The work provides a non-invasive window on how feedback and feedforward circuitry in the human brain operates. We deem the work of potential interest to a broad audience as it aims to provide direct links between the animal invasive electrophysiology and human neuroimaging fields. However, in its current form, major reservations with respect to the hypothesis space being explored here as well as important analytic and technical caveats remain.

(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 #3 agreed to share their names with the authors.)

Evaluation Summary:

This paper examines the visual-ocular response in participants when exposed to the static magnetic field of a 3T MRI system. Historically, this problem has been approached from a safety perspective. In the present study, the authors ask about the behavioral consequences of this field given that it induces a response in the vestibular system, hypothesized to mimic that of a caloric vestibular stimulation event. As such, one should anticipate a biased vestibulo-ocular reflex in the static field as well as biases in spatial attention. These predictions were confirmed, with the attentional bias manifest in eye movements during a visual search task. This is an important finding because it reveals functional "artifacts" that may arise during fMRI studies, effects that may need to be considered by those conducting research in the MR environment (especially functional studies).

(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 names with the authors.)

Evaluation Summary:

The question investigated - to understand the computational significance of different types of local interneurons in neural circuits - is an important and significant problem. Here authors elucidate the role of the two types of LNs, by combining whole-cell patch clamp recordings with calcium imaging via single cell dye injection. This method enables them to monitor calcium dynamics of the different axons and branches of single LNs in identified glomeruli of the antennal lobe, while the membrane potential can be recorded at the same time. They conclude that non-spiking LNs with graded responses show glomerular restricted responses to odorants and spiking LNs show similar responses across glomeruli.

(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 will be of interest to neuroscientists in the fields of spinal motor control and spinal cord injury. The finding that silencing of spared lumbar to cervical long ascending propriospinal neurons after spinal cord injury enhances locomotor coordination is unexpected and well-supported by the data. This has potential implications for strategies aimed at promoting recovery of function after SCI.

(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:

Calcium-calmodulin (CaM) signaling plays an essential role within and outside of the nervous system. Moreover, it is conserved from plants to humans. While a lot is known about the mechanisms of cellular calcium level fluctuations, how CaM levels are regulated is less clear. In this manuscript, Vuong-Brender and colleagues characterize a, likely, conserved role of the transcription factor CAMT-1 in the homeostatic regulation of CaM levels and show how it impacts animal behavior and nervous system function. The paper is a tour-de-force across multiple techniques and model systems. The data is of a very high quality and supports most of the authors' claims strongly and convincingly.

(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 the study presented here, the authors used the fruitfly Drosophila melanogaster to identify a new molecular regulator - the E3 ubiquitin ligase Thin - of presynaptic homeostatic plasticity (PHP), a process where synaptic signaling between motorneurons and muscle cells is dynamically adapted to compensate exogenously imposed changes in synapse strength. Based on a very substantial set of high quality data, the authors propose that Thin functions presynaptically during PHP, that presynaptic thin negatively regulates neurotransmitter release under baseline conditions by limiting the number of release-ready synaptic vesicles, and that Thin controls transmitter release by regulating Dysbindin, a schizophrenia-susceptibility gene required for PHP. The authors' conclusion is that Thin links protein-degradation-dependent proteostasis of Dysbindin to homeostatic regulation of neurotransmitter release. The major claims of the paper are well supported by the data, but alternative hypotheses cannot yet be unequivocally excluded.

(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 #3 agreed to share their names with the authors.)

Evaluation Summary:

In this work, Minh Nguyen and colleagues performed single nuclear RNAseq of human dorsal root ganglion (DRG) neurons and classified them into 15 clusters. A bioinformatic comparison to mouse lumbar DRG single nucleus sequencing results is also described. The importance of reporting the single nucleus or single cell molecular profiles of human DRG cannot be overstated. Proper molecular targeting of therapeutics requires knowing this information. Given that the field is just starting to understand the human specific molecular signature of primary somatosensory neurons using single cell/nuclear RNAseq, this study is important and timely, providing one of the first gene expression databases of individual human DRG neurons.

(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:

Local recycling of synaptic vesicles is required to maintain neurotransmission via clathrin-mediated endocytosis and clathrin-independent ultrafast endocytosis. Clathrin also plays a role in ultrafast endocytosis to regenerate vesicles from a recycling endosome. Here the authors have further tested the role of clathrin and clathrin adaptors in synaptic vesicle endocytosis. This paper raises the interesting possibility that adaptor protein AP-2 but not clathrin contributes to the endocytosis of synaptic vesicle proteins. There are some concerns about differential knockdown of clathrin and AP-2 but if the authors can resolve these, this would be an important result.

(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 authors demonstrate deficits in perceptual tests related to fine-time perception in non-speech and speech sounds in a group of patients with stroke aphasia compared to a control group without a lesion. An area in left auditory cortex is defined that is essential for fine-time perception that is shown in a separate group of normal subjects to other areas including the cerebellum. The work in interesting in suggesting an anatomical basis for interaction between cortical and cerebellar system for perceptual timing.

(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.)