Neuroscience

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:

The precise, simple and non-interfering visualization of neuronal key structures is a major challenge and currently limiting the advancement of our understanding of brain function. This work presents intrabodies as selective and non-interfering tools for the visualization of PSD95 - a major scaffold of the neuronal excitatory postsynapse. This is an important and well executed work that provides an excellent new tool to study an important synaptic molecule.

(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 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.)

Evaluation Summary:

The authors studied the neural correlates of planning and execution of single finger presses in a 7T fMRI study focusing on primary somatosensory (S1) and motor (M1) cortices. BOLD patterns of activation/deactivation and finger-specific pattern discriminability indicate that M1 and S1 are involved not only during execution, but also during planning of single finger presses. These results contribute to a developing story that the role of primary somatosensory cortex goes beyond pure processing of tactile information and will be of interest for researchers in the field of motor control and of systems neuroscience.

(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 is of interest to scientists within the field of lifespan developmental neuroscience. The data analysis is rigorous and the conclusions are justified by the data. The key claims of the manuscript are directly related to, and support, a more reasonable interpretation of previous known findings.

(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 describes the transcriptome and synaptogenic function of astrocytes in the developing visual cortex (VC), a widely used model for neural development. The central questions examined are two-fold: 1) deciphering layer specific organization of astrocytes and 2) how neuronal activity can influence layer specific astrocyte profiles that relate to synaptogenic gene families. Using bulk RNAseq and detailed histology, they demonstrate that expression of key synaptogenic genes are timepoint and layer specific during development, providing an essential resource for understanding how astrocytes change and impact the development of VC circuits. Moreover, the authors revealed that expression of synapse-regulating genes is also regulated by input from thalamic neuronal activity (using vGlut2 KO mice) and astrocyte calcium activity in vivo (using IP3R2 KO mice). They further demonstrate astrocyte molecular changes using snRNA-seq in VGlut2 cKO and Ip3r2 cKO mice. Collectively, these results show that neuronal activity drives the changes in astrocyte function and layer-specific expression of synaptogenic secreted proteins. Overall, this a rigorous and well conducted study that provides important and new information on astrocyte diversity, neuron-astrocyte interactions during development, and mechanisms underlying the expression of key astrocyte synaptogenic genes.

(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 authors use numerical simulations and analyses of neural data from non-human primates to investigate whether rotational dynamics in motor cortical population activity which are typically attributed to recurrent connections can alternatively be explained by sensory feedback alone. They find that neural networks performing the same tasks will produce rotational dynamics even without any internal recurrent units. Overall, this paper examines an important question in the motor control field. The authors should clarify in more detail how the case with no recurrent dynamics has been simulated and address/discuss the role of task structure in their conclusions. Once the authors address issues associated with precisely how they eliminated recurrence from their simulations, the results that rotational dynamics are not necessarily generated autonomously due to recurrent connections will be a valuable and important addition to the ongoing debate about the nature of these rotational 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. The reviewers remained anonymous to the authors.)