Neuroscience

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.)

Evaluation Summary:

This paper claims to identify a long-sought ligand for the receptor protein tyrosine phosphatase Lar that mediates its functions in neuromuscular junction development, mushroom body development, and photoreceptor axon targeting. If correct, this would be of interest to many developmental neurobiologists, However, further evidence is needed to strongly support this claim.

(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 study shows how astrocytic MCL1 can contribute to postnatal maturation of the brain vascular system. Since the development and physiological roles of perivascular astrocyte coverage are not well understood, this manuscript provides potentially important frame works and should be of interest to the broad fields of neuroscientists.

(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 names with the authors.)

Evaluation Summary:

This work from Xu et al. uses state of the art viral tracing technologies in Cre-transgenic mouse lines to map the inputs and outputs of glutamatergic and GABAergic neuronal populations in the dorsal (DR) and median raphe (MR) nucleus. A large amount of high-quality anatomical dataset was collected with the advanced fMOST whole-brain imaging system. Data analysis was thorough with significant scientific insights. All figures are of high quality. Overall, this study nicely complements previously published work on whole-brain connectivity of the DR and MR which have chiefly focused on the main neuromodulatory neurons found in these nuclei, i.e. serotonin and dopamine neurons, and will be a valuable contribution to understanding neural circuits of the raphe system.

(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 reports that monocular inactivation of the fellow (good) eye with tetrodotoxin supports long-lasting recovery from the effects of monocular deprivation, as measured by visual evoked potentials in primary visual cortex. This work should be of interest to neuroscientists studying plasticity and clinicians treating amblyopia. The results are compelling, although the advance compared to previous work is incremental.

(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 will be of interest to scientists working on adult Drosophila behavior, especially as it relates to a region called subesophageal zone. This area is an important integration center for different nervous system functions, including taste information processing and motor control of mouth parts and body movements. Specifically, it provides genetic tools (sparse gal-4 lines) that target different cell types in the subesophageal zone for future functional analysis.

(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.)