Neuroscience

Evaluation Summary

This study investigates the question of whether distinct brain areas differentially encode time during the learning of a simple motor timing task. The key novel result is that early in training the dynamics of the medial prefrontal cortex (mPFC) provides the best code for time, but later in training, the basal ganglia and in particular, the striatum provides a better code. In addition, the study shows that inactivation of mPFC produces a delayed learning effect, while inactivation of the striatum after learning led to impaired performance. The observation that temporal coding and the necessity of brain area for task performance transfers from medial prefrontal cortex to the striatum during learning is an intriguing observation for our understanding of the neural mechanisms underlying temporal processing in sensorimotor control.

(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, contains fundamental findings that substantially advance understanding of an important research question, mostly uses appropriate and validated methodology in line with the current state-of-the-art, with good support for the claims, and the message of the manuscript will have a profound and lasting influence on neuroscience. In essence, the manuscript reports that dopamine converts spike-timing-dependent synaptic depression into potentiation that requires cAMP/PKA second messenger cascade and protein synthesis. The mechanism enables a separate synaptic input to induce heterosynaptic potentiation in previously primed synapses, which is shown in a network model to have desirable computational properties. The significance of the findings is threefold: First, it is the longest-lasting synaptic eligibility trace identified so far; second, the mechanism enables memory linking between temporally separate events; and third, it indicates a novel function of postsynaptic reactivation events. In addition, the finding may inspire new reinforcement learning algorithms in machine learning.

(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 paper establishes a visually mediated gap-jumping behavioral task in freely moving mice, and shows that mice can perform the task using only monocular cues with little performance deficit, perhaps at the cost of additional active sensing movements before executing the jumping maneuver. Further, using acute optogenetic inhibition, the authors establish that the primary visual cortex is used to perform this task. Using vision to judge distance - such as the width of a gap to be crossed - is crucial for survival across taxa, and this new paradigm could be informative to those interested in using mice to study such vision-based estimation under naturalistic conditions.

(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 researchers in the fields of motor control, visual perception, learning and brain plasticity, sight loss and rehabilitation. The paper shows the contributions of sensory-motor experience to the development of visuo-motor recalibration abilities using careful experimental methods and analyses, comparing a rare population of late-operated cataract patients with control groups.

(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 role of satellite glial cells in the sympathetic nervous system has not been extensively investigated. Using targeted ablation of SGCs, the authors demonstrate that satellite glia has a profound effect on neuronal activity and the survival of sympathetic neurons. The peripheral sympathetic system is responsible for a wide spectrum of activities, including blood flow, heart rate, respiration, and digestion.

(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:

Kikumoto and colleagues explore the question of how stimulus- and response-related mental representations are stored and selected in working memory. The authors use a combination of decoding and representational similarity analysis on EEG data to provide evidence for conjunctive representations of action plans. This work would potentially be of great interest to readers in the field of working memory, motor preparation, and selective attention.

(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 presents an exploitation/exploration paradigm using a model-based approach in 18 patients treated with GPi DBS for Tourette's syndrome. Their main observation is that despite DBS (used as a proxy of GPi inhibition) doesn't have any effect on the overall performance of the subjects, it has a significant effect on the probability of exploration. This work will be interesting for scientists working in fundamental and clinical neurosciences.

(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 manuscript is of broad interest to readers in the field of Alzheimer's disease, neurodegeneration, and single-cell omics. The identification of shared pathways across different cell types and ages is an important contribution to our understanding of APOE4 gene regulation in a cell type-specific manner. A combination of snRNAseq in APOE mouse models and human iPSC cells supports the key claims in the paper.

(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 presents novel experimental data from a mutant mouse model lacking microglia (Pu.1-/- mouse line), indicating that these cells have an important role in the embryonic establishment of critical neural circuits in the brainstem generating breathing motor behavior in mice. This paper is of interest to scientists within the field of microglia as well as respiratory neurobiology as it provides original key information about a new role of microglia in the embryonic development of respiratory circuits. Overall, the data are clearly presented and rigorous. Some of the conclusions should be toned down as the data in another microglia depletion model do not support some claims of the paper.

(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 name with the authors.)

Evaluation Summary:

The current manuscript presents a computational model of numerosity estimation. The model relies on center-surround contrast filters at different spatial scales with divisive normalization between their responses. Using dot arrays as visual stimuli, it is shown that the summed normalized responses of the filters are sensitive to numerosity and insensitive to the low-level visual features of dot size and spacing. Importantly, the model provides an explanation of various spatial and temporal illusions in visual numerosity perception.

(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.)