Neuroscience

Subjective time is predicted by local and early visual processing

1. Yelena Tonoyan
2. Michele Fornaciai
3. Brent Parsons
4. Domenica Bueti

• Curated by eLife

  Summary: This work uses electro-encephalographic (EEG) recordings combined with an interesting experimental approach to measure temporal expansion/compression. Specifically, the question addressed here is whether adaptation to visual motion affects perceived duration, and if so, how spatially confined these effects are with respect to the processing of the stimulus in early visual areas. The authors find consistent evidence that a visual reference is judged as shorter/longer depending on a previous adaptation. They report several EEG analyses suggesting the early visual activity is correlated with such temporal distortions. This manuscript is of potential interest to cognitive neuroscientists specifically interested in temporal aspects of visual processing and time perception. Although the paradigm is well suited to assess the authors' question, the behavioral data as well as the electrophysiological analyses show important shortcomings currently hindering the interpretation of the results, and necessitating substantial revisions to the current work. Additionally, further methodological details are required to strengthen the manuscript.

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Heritable functional architecture in human visual cortex

1. Ivan Alvarez
2. Nonie J. Finlayson
3. Shwe Ei
4. Benjamin de Haas
5. John A. Greenwood
6. D. Samuel Schwarzkopf

• Curated by eLife

  Evaluation Summary:

  The paper was viewed as generally sound. There main concern was that the findings were viewed as incremental without a demonstration of a link between the heritability of pRF properties and visual perception. The speculation in the Discussion about shared perceptual experience is intriguing, but psychophysical (or other) evidence would be needed to really make that point clearly. In addition, there was some discussion about the non-independence of vertices and correlation values. In the end, we all agreed that non-independent vertices may inflate correlation coefficient values, but that this is unlikely to substantially affect conclusions drawn from comparisons of monozygotic and dizygotic twins.

  (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.)

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Unveiling the sensory and interneuronal pathways of the neuroendocrine connectome in Drosophila

1. Sebastian Hückesfeld
2. Philipp Schlegel
3. Anton Miroschnikow
4. Andreas Schoofs
5. Ingo Zinke
6. André N Haubrich
7. Casey M Schneider-Mizell
8. James W Truman
9. Richard D Fetter
10. Albert Cardona
11. Michael J Pankratz

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of broad interest to readers in the field of neuroscience. The authors use a serial section transmission electron microscopy data set to trace out the entire neuroendocrine system of a maggot from its sensory input to neuroendocrine cells. It highlights the complexity of brain circuits, describing how parallel processing systems can lead to a multitude of different input combinations for different neuroendocrine cell types and subcircuits. They provide interpretations about functionality of one of described neural circuits. While the analyses are generally rigorous, the functional interpretations need more supporting evidence.

  (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.)

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Prenatal methadone exposure disrupts behavioral development and alters motor neuron intrinsic properties and local circuitry

1. Gregory G Grecco
2. Briana E Mork
3. Jui-Yen Huang
4. Corinne E Metzger
5. David L Haggerty
6. Kaitlin C Reeves
7. Yong Gao
8. Hunter Hoffman
9. Simon N Katner
10. Andrea R Masters
11. Cameron W Morris
12. Erin A Newell
13. Eric A Engleman
14. Anthony J Baucum
15. Jiuen Kim
16. Bryan K Yamamoto
17. Matthew R Allen
18. Yu-Chien Wu
19. Hui-Chen Lu
20. Patrick L Sheets
21. Brady K Atwood

• Curated by eLife

  Evaluation Summary:

  This work studied mice that had already taken oxycodone that then were switched to methadone treatment prior to becoming pregnant, to model prenatal methadone exposure (PME). The experimental design featured a study of a wide array of measures in the next generation progeny: including physical development, sensorimotor behavior, vocalizations, brain imaging, electrophysiology, and histology. All three reviewers agreed this work provides a novel, thorough, and highly clinically-relevant model of PME that has high value to the field of neuroscience of addictions and developmental neuropharmacology.

  (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.)

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TRPM channels mediate learned pathogen avoidance following intestinal distention

1. Adam Filipowicz
2. Jonathan Lalsiamthara
3. Alejandro Aballay

• Curated by eLife

  Evaluation Summary:

  In this manuscript, the authors aim to address an important and interesting question: when an animal's intestine is colonized by pathogenic bacteria, how can it sense these bacteria and learn to avoid consuming them? Here the authors suggest that in C. elegans, sensing of intestinal distension or bloating caused by Gram-positive bacteria via intestinal ion channels may drive rapid behavioral responses through a process involving associative learning. While these findings are of broad interest to both the microbiology and neurobiology community, some of their conclusions are not currently fully supported by their data, and reasonable alternative interpretations exist.

  (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.)

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Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

1. Inés González-Calvo
2. Keerthana Iyer
3. Mélanie Carquin
4. Anouar Khayachi
5. Fernando A Giuliani
6. Séverine M Sigoillot
7. Jean Vincent
8. Martial Séveno
9. Maxime Veleanu
10. Sylvana Tahraoui
11. Mélanie Albert
12. Oana Vigy
13. Célia Bosso-Lefèvre
14. Yann Nadjar
15. Andréa Dumoulin
16. Antoine Triller
17. Jean-Louis Bessereau
18. Laure Rondi-Reig
19. Philippe Isope
20. Fekrije Selimi

• Curated by eLife

  Evaluation Summary:

  The reviewers agreed that this is a very interesting paper that demonstrates the involvement of a specific protein degradation pathway in a form of synaptic plasticity in the cerebellum. The strength of the work results from its innovative character. The authors show that SUSD4 is expressed throughout the brain and is abundant in cerebellar dendrites and spines. Mice with deletion of SUSD4 have motor coordination and learning deficits, along with impaired LTD induction. This study provides novel insight in the uncharacterized role of SUSD4 and provides a detailed and well-performed analysis of the Susd4 loss of function phenotype in the cerebellar circuit. The exact mechanism by which SUSD4 affects GluA2 levels remains unclear. However, their findings provide leads for further functional follow-up studies of SUSD4.

  (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.)

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Differential effects of amplitude-modulated transcranial focused ultrasound on excitatory and inhibitory neurons

1. Duc T. Nguyen
2. Destiny Berisha
3. Elisa Konofagou
4. Jacek P. Dmochowski

Reviewed by eLife

Diverse inhibitory projections from the cerebellar interposed nucleus

1. Elena N Judd
2. Samantha M Lewis
3. Abigail L Person

• Curated by eLife

  Evaluation Summary:

  Judd and colleagues use a combination of mouse genetics and viral marking to expand the extra-cerebellar map of projections. These data will impact our understanding of how the cerebellum contributes to behavior and in general how brain function is packaged at the anatomical level. These data will not only impact cerebellar scientists but also those workers interested in how inter-regional brain connectivity is organized and how fine input-output circuit relationships are structured.

  (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.)

Reviewed by eLife

The structure of behavioral variation within a genotype

1. Zachary Werkhoven
2. Alyssa Bravin
3. Kyobi Skutt-Kakaria
4. Pablo Reimers
5. Luisa F Pallares
6. Julien Ayroles
7. Benjamin L de Bivort

• Curated by eLife

  Summary: This manuscript is interesting to circuit-neurobiologists, behavioural biologists and psychologists. The reviewers agree that this manuscript addresses an important unanswered question: what is the covariation-structure in the vast space of behavioural variables that individuals can explore, and what defines their individuality in this space? The reviewers also praise the great efforts made in the experimental approach and analyses methods, which potentially will set new benchmarks in the field. However, the work can be improved, by accounting for the trial-to-trial variability in behavioural data and clearly distinguishing these from persistent idiosyncrasies observed in individuals.

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Functional spreading of hyperexcitability induced by human and synthetic intracellular Aβ oligomers

1. Eduardo J. Fernandez-Perez
2. Braulio Muñoz
3. Denisse A. Bascuñan
4. Christian Peters
5. Nicolas O. Riffo-Lepe
6. Maria P. Espinoza
7. Peter J. Morgan
8. Caroline Filippi
9. Romain Bourboulou
10. Urmi Sengupta
11. Rakez Kayed
12. Jérôme Epsztein
13. Luis G. Aguayo

• Curated by eLife

  Summary: This study provides new information about how amyloid beta (Ab) oligomers (Abo) may contribute to hyperexcitability which is important because Abo and hyperexcitability have been suggested to occur early in the development of Alzheimer's disease (AD). The authors added Abo intracellularly (iAbo) using dialysis from a patch pipette. Their data suggest iAbo led to increased synaptic excitation mediated presynaptically by retrograde signalling of nitric oxide (NO). Furthermore, they present data suggesting that there is spread of this increase in excitation to neighboring neurons.

  Major Comments:

  1. The nature of the described effects of intracellular iAbo are quite unexpected, occurring within a minute of obtaining intracellular recording configuration, which contrasts with at least on previous study. While some controls for intracellular application of oligomers are provided, with reverse iAbo failing to reproduce the effect (Fig 2S1) and the effect being blocked by the antibody A11 (Fig 2S2), further controls are necessary to explain this rapid effect, which seems faster than that for the diffusion of the fluorescent tag into the cell (Fig 1S1). Note that Pusch and Neher (Pflug Arch 1988) determined diffusion time for different substances. That paper or others should be cited, and then some estimation of equilibrium time based on diffusibility of ab oligomers should be provided. Equations 17 and 18 in that paper provide some estimates based on molecular weight or diffusion coefficient. One point in Pusch and Neher is there is extreme variability between access times across cells and that it depends on access resistance, of course. Finally, the Pusch and Neher calculations were for small spherical cells - diffusion into spatially extended cells with long dendrites where the synapses are will take even longer. This is especially critical, as one of the major papers of precedent for this work is that of Ripoli, et al. 2014 (cited in the manuscript) in which the authors of that work examined effects of patch applied Ab42 over the course of 20 minutes, with internal controls showing differences between initial responses, right after break in, and 20 minutes later when the oligomer and/or monomers will have had a chance to equilibrate with the intracellular contents. It is not clear how such a rapid effect as indicated in the figures could be achieved by such a large molecule as Ab. The data suggest a time to effect of seconds to minutes, and the peak effect occurs before the fluorescence peaks, which seems hard to explain.

  2. The data need reorganization in terms of their results using h-iAbo or iAbo. There needs to be a clear demonstration of why both were used if the results are generalized with both (or not) and if they can actually use both interchangeably.

  3. The authors need to clearly indicate whether the experiments were done in culture or in slices. The authors need to provide a rationale on why specific experiments were done in culture and others in slices.

  4. There are aspects of the observed phenomenon that have not been taken adequately into account. For example, the authors have not investigated the effects of application of oligomeric beta-amyloid to either the extracellular space or the presynaptic neurons, two other compartments of the synapse.

  5. Aspects of the data raise questions: 1) Western blots appear to have multiple bands 2) evidence that the fluorescent probe accurately measures NO. 3) The bursts of activity are not quantified. What was defined as a burst? What was the burst frequency and did it change over the recording period? 4)The external solution for cultures contain 5.4 mM K+ which is quite high, and can induce hyperexcitability. Similarly, the use of 100uM AMPA and GABA seem very high. Justifying these high concentrations is important. They should lead to hyperexcitability and toxicity (AMPA) over time. Another point of concern is that the concentration of K+ for the slice work is 3 mM, much different than cultures. There are also differences in Mg2+ and Ca2+, making data hard to compare in the two preparations. 5) sample sizes are unclear 6) Intracellular Ab produces increases in both EPSCs and IPSCs. However, in Fig 3, the IPSC measures using a charge transfer quantification, did not show a significant change in response to iAbo, in contrast to EPSCs. 7) With regard to the inhibition, In the schematic on Fig. 10, I find this incomplete and slightly inaccurate since it shows one terminal releasing both glutamate and GABA with NO increasing both. While this is obviously an oversimplification, it's slightly inaccurate since NO was not directly shown to increase sIPSCs. Were NOS blockers able to disrupt the increase in sIPSCs? Moreover, there are many papers that have shown that PKC can also phosphorylate GABA receptors and increase their conductance. What could be the reason that this was not involved here? This needs to be discussed.

  6. How this work relates to other studies is necessary. For example, how this study is related to others about Ab exposure is lacking. Also, regarding hyperexcitability, many possible causes exist. These should be summarized in the introduction and the authors should comment how their results fit with these studies. Regarding PKC and NO, PKC and NO have several known actions throughout the brain and body. How do the effects the authors have identified relate to all these other effects? For example, if PKC is activated by another mechanism, would it occlude effects of Ab? What are the changes in PKC and NO in AD? Regarding the ability of the data to address AD, a major issue is whether the results are relevant to AD or represent interesting pharmacological data about what Ab can potentially do in some of its forms in normal tissue.

  Reviewer #2 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife