Neuroscience

Evaluation Summary:

Zobeiri and Cullen address the important question of how the cerebellum transforms multiple streams of sensory information into an estimate of the motion of the body in the world. They find that Purkinje cells, the inhibitory principal neurons of the cerebellar cortex, have multimodal and highly diverse responses to vestibular and neck proprioceptive inputs. Notably, this information is combined in a way that is different than what is seen in downstream fastigial neurons, which reflect either head or body motion, but not both. The experiments are well executed, generating data that provide important and novel insights, but there are shortcomings in the model put forward to account for these 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

Reich and colleagues have combined MRI imaging and histopathology to study the remyelination of brain lesions in an EAE marmoset model of multiple sclerosis. This work addresses in a non-human primate a missing link in the neuropathology of myelin repair, because in human MS it is virtually impossible to study the lesion dynamics by MRI (in live patients) and demyelination by histology (upon brain autopsy). The present manuscript would be improved by adding further histological evidence of remyelination and clarifying open questions of data acquisition.

(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 is of interest to scientists within the field of motor control and learning. The experiments provide novel insight into the potential role of associative learning in sensorimotor adaptation. The results are compelling, although further data are required to support several key conclusions.

(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:

Synaptic plasticity typically requires the conjunction of dendritic action potentials and synaptic activation. Together these signals cause nonlinear changes in calcium influx that then drive plasticity. The strength of these interactions can vary in complex ways. The authors use an elegant combination of imaging and electrophysiology to convincingly show how some of these complexities in murine cortical neurons arise from electrical properties of neuronal dendrites and synaptic NMDA receptors. This is a thorough and well done analysis of a set of issues that have implications for the ways in which dendritic morphology affect plasticity "rules." The underlying principles are largely previously understood, but their implications (e.g. the difference between voltage dependence of calcium channel and NMDA receptor calcium influx) are not widely appreciated and yet have important effects on the resulting integration.

(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 utilizes a miniscope approach and GCaMP6 in freely behaving conscious mice to record CO2-associated multicellular calcium responses of neurons or glia in brainstem regions implicated in CO2-dependent control of breathing. The application of this approach in this context is extremely attractive, and new to the respiratory neurobiology field. Several technical improvements could strengthen the manuscript. Foremost, the study is broad in scope and consequently not always technically rigorous in important aspects such as identification of cell types imaged. In some cases that affects interpretation of the significance of the results. Since some of the conclusions about cellular responses to CO2 are mostly at odds with a substantial literature using more established techniques, there is even greater onus on the authors to ensure reliability of the 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 #1 agreed to share their name with the authors.)

Evaluation Summary:

Given the well-known importance of the SYNGAP1 mutations in the pathophysiology of neurodevelopmental disorders and the key regulatory roles of SynGAP1 for excitatory synaptic functions, this study provides timely and comprehensive sets of data supporting the in vivo functions of individual SynGAP1 splice variants, including the alpha-1/2 variants, and suggests the therapeutic potential of increasing specific SynGAP1-alpha variants.

(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 is an interesting quantitative study of the anatomical connections of a region of prefrontal cortex that has often been overlooked - the Ventrolateral Prefrontal Cortex. The idea that this is a special region that is different to both the rest of ventrolateral prefrontal cortex and probably the rest of orbitofrontal cortex is important because it helps us understand some otherwise puzzling results. The quantitative analysis of connections is an unusual strength of the study as is the comparison of tracer data in macaques, fMRI connectivity data in macaques, and human fMRI connectivity data.

(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 employs sophisticated modeling of human behavior in well-controlled tasks to study how limitations of working memory constrain decision-making. Because both are key cognitive processes, that have so far largely been studied in isolation, the paper should be of broad interest to neuroscientists and psychologists. The observed working memory limitations support and extend previous findings, but some of the most interesting claims need additional support.

(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:

Soyman and colleagues investigate intensity coding for the "pain of others" in the human insula with intracranial human recordings. Additional data of a related fMRI study is analyzed and discussed in the context of the intracranial data. The paper addresses an important research question of broad interest, with extremely unusual data which is investigated in considerable detail.

(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:

Morozova et al. describe potential mechanisms contributing to the flexibility of burst patterns and dynamic responses to perturbations within an isolated reciprocally inhibitory circuit derived from the stomatogastric ganglion of the crab. The authors use the dynamic clamp approach to study the interactions between pharmacologically isolated, intrinsically silent gastric mill neurons, an approach pioneered by Andrew Sharp in the 1990s. The authors demonstrate that the mechanisms of switching between components of the reciprocally organized half-center network are not fixed and may shift to favor a release or escape mechanism depending on factors such as the synaptic threshold, Ih conductance, and synaptic conductance. This is a fundamentally important study because reciprocally organized networks are ubiquitous and found virtually in every organism. It is assumed that this half-center-type network organization governs rhythmic activity with a wide range of functions.

(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. Reviewers #1, #2 and #3 agreed to share their names with the authors.)