Neuroscience

Evaluation Summary:

This paper addresses the very extremely interesting question of how spontaneous activity in the cochlea prior to hearing onset impacts the development of auditory circuits in the brainstem. The study has many strengths, including the use of complementary in vitro and in vivo recording techniques to characterize both peripheral and central defects resulting from conditional deletion of the gene for the chloride channel TMEM16A. The reviewers identified some concerns over the interpretation of the data and felt that the results could be discussed more in the context of other work, which might require some additional experiments.

(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:

Aggregates of the protein Tau are a key pathological features of Alzheimer's Disease and several other neurodegenerative disorders (Tauopathies). Hori et al. examined the effects of an acute elevation of Tau levels in synapses, employing high-end paired pre-post-synaptic patch-clamp recordings at the Calyx of Held model synapse. The authors generated a technically very rigorous dataset indicating that increased levels of soluble Tau impair pre-synaptic endocytosis and, consequently, neurotransmission by sequestering Dynamin-1 on microtubules, and propose that this process is part of a synaptic manifestation of Tauopathies. The findings are of major relevance for basic neuronal cell biology and translational neuroscience alike. However, several aspects of the proposed molecular mechanism underlying the synaptic effects of elevated Tau levels remain less clear.

(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 examines model neuron solution sets - combinations of ionic membrane conductance parameters that allow the model to produce functional output properties - and how the extent and shape of these solutions sets depends on ion channel pleiotropy, i.e., that ion channels can influence multiple outputs simultaneously. The work provides an organizing framework for previous experimental and modeling studies related to degeneracy of solutions, ion channel correlations, and homeostatic regulation, and should therefore be of interest to researchers in this area.

(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 uses a powerful combination of imaging techniques to provide a thorough view of the structure of the gap junction network connecting rod and cone photoreceptors in the mouse retina. The main conclusion - that rod-cone coupling is much more prevalent than rod-rod or cone-cone coupling - is well supported by the data although some results require qualification. The main concern in review centers around the importance of this result beyond the retina community.

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

Evaluation Summary:

This manuscript features high quality experimental data with a detailed and clear analysis, combined with a neural network model to address the concept of differentiation in cerebellar functioning. This is an intensively debated topic currently and this work has an important, clear message to add to that debate. The data is very exciting, and the analyses and computational modeling very revealing and insightful. This stands on its own as a major contribution. The authors also raise an extremely interesting mechanistic interpretation of these data, which is tantalising but requires further 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper is of interest to scientists within the field of motor learning. Converging evidence from several behavioural experiments support key claims of the paper. However, it is unclear to what degree the reported effects can be strongly linked to motor versus cognitive systems, and to what degree they novel demand revision of existing theoretical frameworks.

(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:

Tworig and colleagues use the mouse retina to explore the motility of Muller glial processes during development and during retinal waves that drive intracellular calcium signals in Muller glia. This is an important topic, because astrocytes in the brain have been suggested to move relative to synapses during neuronal activity. By performing careful and rigorous experiments, the authors find Muller glia processes move during development, but are not driven to move by neuronal activity. This is an important finding that will be of interest to diverse groups of readers.

(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:

Feedforward inhibition (FFI) typically exerts a powerful effect shaping neural activity. In this paper, Suzuki et al use a combination of in vivo and in vitro experiments to characterize, for the first time, responses in the two main classes of FFIs in the mouse olfactory cortex, neurogliaform cells (NG) and horizontal cells (HZ). They find that these two cell types have different responses and different connectivity, which partially explains their different responses. This paper also helps resolve a previously perplexing result from a recent high-profile publication that claimed that FFI in the mouse olfactory cortex appears to play a negligible role in shaping cortical odor responses, presumably because those authors were only recording from HZ cells.

(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:

The research conducted examines how the patterns of human eye-movements recorded during the navigation of complex mazes in immersive virtual reality relates to the computational demands of navigating the mazes. A key result is evidence of sweeps to the goal across the maze and back from the goal towards the current location prior to movement, which may help with understanding computational principles of planning. A key strength is its sophisticated computational measures for characterizing the multiple dimensions of eye movement data and the fact this work is novel with few prior studies investigating this important topic. Its findings and methodology are of interest to many areas within cognitive neuroscience, notably decision making and navigation.

(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 those studying the neuroscience of movement, as it addresses a fundamental aspect of movement: motoneuron recruitment. The authors provide a comprehensive analysis of motoneuron intrinsic properties that mature in the early post-natal period in mice and may lead to differentiation into "slow" and "fast" phenotypes. The authors argue that these properties, studied in spinal cord slices, contribute to motoneuron recruitment. While the study provides insights on the maturation of electrophysiological properties in motoneuron subtypes, the claims related to ionic mechanisms involved in orderly recruitment require further justification.

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