Neuroscience

Evaluation Summary:

This is a challenging study exploring the effects of a commonly used analgesic, remifentanil, on brain and spinal cord related pain processing in humans. It is of considerable interest to the pain research, neuroimaging and opioid neuroscience communities and are also relevant to clinicians who commonly use opioid infusions. The authors have used sophisticated methods for combined brain and spinal cord functional magnetic resonance imaging to examine the influence of an intravenous opioid on pain processing in the ascending and descending pain pathways in healthy subjects. The authors have conducted a comprehensive assessment in large numbers of subjects and have explored both changes in amplitude of activity as well as connectivity. Their detailed analysis strengthens findings from previous human and animal studies and extend to demonstrate novel changes in connectivity in the descending pathway to the spinal cord although these data are potentially compatible with alternative interpretations and may need to be reinforced by further 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:

Giove and colleagues demonstrate an intriguing dissociation of neurovascular (as measured with BOLD-fMRI) and neurometabolic (measured with fMRS) responses during perception. This is a thought-provoking study that makes one wonder about the signals we measure with human neuroimaging, especially fMRI. It will therefore be of great interest to the broad community of neuroimagers, as well as perception researchers.

(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 name with the authors.)

Evaluation Summary:

This paper uses an anatomically-constrained neural network model to investigate how looming visual stimuli - i.e. stimuli likely to collide with an organism - could be detected. The authors find one dominant solution to this problem reproduces both the computational properties and neural responses of known collision detecting neurons in the fruit fly, Drosophila melanogaster, without ever being trained on neural data. Their findings shed light on why biological collision detection circuits may have converged on particular solutions. A similar approach could reveal important computational features in other circuits.

(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:

This manuscript reports a surprising discovery in C. elegans: upon losing its normal sensory properties, the ADL nociceptive/pheromone sensing neuron relays and thereby enhances oxygen behavioral responses via neuropeptide signaling. This effect could be interpreted as cross-modal sensory plasticity or more general a cross-modulation between sensory circuits, a still open question that should be addressed in a revision. The study is relevant to scientists working on sensory neurobiology and neuronal plasticity.

(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 provides strong evidence that adaptation in cone photoreceptors of the primate retina can subtly change the balance of excitatory and inhibitory inputs to On parasol ganglion cells and thereby fundamentally affect how these cells integrate visual information. This study provides important mechanistic insight into the previous observation that On parasol cells display nonlinear spatial stimulus integration under standard reversing gratings but linearly integrate signals in the context of natural scenes. The findings will be of great interest to visual 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 and Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

Using computational modeling and dynamic clamp recordings, this work supports the concept that hyperexcitability of cortical circuits in a familial mouse model of Alzheimer's disease is caused by impairments of biophysical properties of Kv3 channels in parvalbumin-positive cortical interneurons. Overall, the work is clear and interesting but some further analysis is required to provide compelling support to the central claims.

(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 will be of interest to the large class of neuroscientists who investigate brain plasticity. It identifies short-term plasticity in a subcortical region, the ventral division of the pulvinar, following monocular deprivation in adult humans. The work is believed to extend our research focus on the topic of ocular dominance plasticity from mainly the cortex to a larger brain network including the subcortical stages of visual processing. This is an intriguing possibility, but further evidence is required to fully support the claims.

(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 will be of broad interest to readers who study anatomical connections of the brain. It demonstrates the efficacy of a cutting-edge viral tracing technique in mapping excitatory projections in macaque monkeys. The work describes the generation of a projectome from the macaque vlPFC cortex across the rest of the brain using AAV2/9-CaMKIIa-Tau-GFP labeling and imaging with high-throughput serial two-photon tomography. The comparison with imaging techniques available in humans (diffusion tractography) will also be of interest to research in human brain anatomy.

(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 by Yu et al. captures the transcriptional heterogeneity of mouse POMC neurons across hypothalamic development. This study unifies multiple other observations about the role for other neuron al cell types that express POMC transiently during development. The paper is an important resource understanding of the diversity of POMC neuron classes and their relationship to other cell types in the arcuate nucleus.

(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 will be of interest to neuroscientists, particularly those studying defensive behaviors. The authors provide novel insights into the mechanisms by which the brain computes contextual information associated with innate threats in mice. The experimental approach and data analysis are mostly adequate and the study provides the first causal evidence of a hippocampus-anterior hypothalamic pathway mediating spatial fear memory of ethological threats. The implementation of more robust statistical tests, as well as more detailed Methods and Discussion sections should serve to strengthen an already elegant study.

(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 name with the authors.)