Neuroscience

Keratinocyte PIEZO1 modulates cutaneous mechanosensation

1. Alexander R Mikesell
2. Olena Isaeva
3. Francie Moehring
4. Katelyn E Sadler
5. Anthony D Menzel
6. Cheryl L Stucky

• Curated by eLife

  Evaluation Summary:

  This manuscript is of broad interest to readers in the field of somatosensation. The identification that a common type of skin cell responds to mechanical force using a specific molecular receptor called Piezo1 is an important contribution to our understanding of mechanotransduction. A combination of conditional gene knockout with physiological and behavioral assays provides intriguing evidence that communication between skin and nerves is important for normal touch sensation, a conclusion that if further supported by additional data could become a fundamental discovery.

  (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.)

Reviewed by eLife

Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment

1. Yanan Chen
2. Rejani B Kunjamma
3. Molly Weiner
4. Jonah R. Chan
5. Brian Popko

• Curated by eLife

  Evaluation Summary:

  This is an elegantly conducted study showing integrated stress response (ISR) contributes to protection of oligodendrocytes in the remyelination process in the setting of an inflammatory environment. The authors use both genetic (GADD43KO) and pharmacological approaches (Sephin1) to study ISR in demyelination animal models. The data are convincing and have important clinical implications for multiple sclerosis and other diseases. The reviewers agree that revisions are needed for the sake of presentation, clarity, rationale, and interpretation of datasets.

  (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.)

Reviewed by eLife

Temporal pattern and synergy influence activity of ERK signaling pathways during L-LTP induction

1. Nadiatou T Miningou Zobon
2. Joanna Jędrzejewska-Szmek
3. Kim T Blackwell

Reviewed by eLife

Decoding subjective emotional arousal from EEG during an immersive virtual reality experience

1. Simon M Hofmann
2. Felix Klotzsche
3. Alberto Mariola
4. Vadim Nikulin
5. Arno Villringer
6. Michael Gaebler

• Curated by eLife

  Summary: Hofmann et al. investigate the link between two phenomena, emotional arousal and cortical alpha activity. Although alpha activity is tightly linked to the first reports of electric activity in the brain nearly 100 years ago, a comprehensive characterization of this phenomenon is elusive. One of the reasons is that EEG, the major method to investigate electric activity in the human brain, is susceptible to motion artifacts and, thus, mostly used in laboratory settings. Here, the authors combine EEG with virtual reality (VR) to give experimental participants a roller-coaster ride with high immersion. The ride, literally, leads to large ups and downs in emotional arousal, which is quantified by the subjects during a later rerun. Three different decoding methods were evaluated (Source Power Comodulation, Common Spatial Patterns, and Long Short-Term Memory Recurrent Neural Networks), each of which demonstrated above-chance levels of performance, substantiating a link between lower levels of parietal/occipital alpha and subjective arousal in a quasi-naturalistic setting.

  The reviewers both expressed some enthusiasm for the MS:

  The study is timely and makes an important contribution to our understanding of the relation of emotions and sensory processing

  Of potentially great interest to a broad audience

  The embedding in historic literature is excellent. I like it a lot.

  This work is notable because the roller-coaster simulation is a well-controlled, yet dynamic manipulation of arousal, and in its comparison of multiple decoding approaches (that can model the dynamics of affective responses). Indeed, this is an interesting proof of concept that shows it is possible to decode affective experience from brain activity measured during immersive virtual reality.

  Reviewer #1 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans

1. Trygve E Bakken
2. Cindy TJ van Velthoven
3. Vilas Menon
4. Rebecca D Hodge
5. Zizhen Yao
6. Thuc Nghi Nguyen
7. Lucas T Graybuck
8. Gregory D Horwitz
9. Darren Bertagnolli
10. Jeff Goldy
11. Anna Marie Yanny
12. Emma Garren
13. Sheana Parry
14. Tamara Casper
15. Soraya I Shehata
16. Eliza R Barkan
17. Aaron Szafer
18. Boaz P Levi
19. Nick Dee
20. Kimberly A Smith
21. Susan M Sunkin
22. Amy Bernard
23. John Phillips
24. Michael J Hawrylycz
25. Christof Koch
26. Gabe J Murphy
27. Ed Lein
28. Hongkui Zeng
29. Bosiljka Tasic

• Curated by eLife

  Summary: This manuscript provides a comparative analysis of the cell variety present in the dorsal lateral geniculate nucleus (dLGN) of mice, non-human primates, and humans using single-cell/single-nucleus RNA-sequencing (Smart-seq). The study identifies excitatory and inhibitory dLGN cell types in the three species and shows that the different subclasses of inhibitory neurons are relatively similar across species. In contrast, excitatory neurons appear to bear cross-species differences particularly between mouse and primates. The study provides an extensive description of the dLGN neurons, an important visual relay nucleus that has been so far poorly studied. As such, these data are very welcomed and will likely attract the interest of researchers working in visual function and beyond. The strong and creative bioinformatics analysis has uncovered interesting and subtle cross species links between different types of neurons.

  Reviewer #1, Reviewer #2 and Reviewer #3 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

Perception of microstimulation frequency in human somatosensory cortex

1. Christopher L Hughes
2. Sharlene N Flesher
3. Jeffrey M Weiss
4. Michael Boninger
5. Jennifer L Collinger
6. Robert A Gaunt

• Curated by eLife

  Evaluation Summary:

  This paper characterizes percepts evoked by micro-stimulating the somatosensory cortex of a human participant. The study provides some new insight into the organization of the human somatosensory cortex and represents an important step in providing more effective somatosensory feedback for brain-machine interface users.

  (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 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

Anticipation of temporally structured events in the brain

1. Caroline S. Lee
2. Mariam Aly
3. Christopher Baldassano

• Curated by eLife

  Evaluation Summary:

  The study addresses a topic that is timely and of general interest. The findings represent a potentially very interesting contribution to the important question of how the brain comes to predict the future, in particular lifelike sequences of events. However, some of the main conclusions would require further statistical 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.)

Reviewed by eLife

Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN

1. Wanhui Sheng
2. Scott W Harden
3. Yalun Tan
4. Eric G Krause
5. Charles J Frazier

Reviewed by eLife

Rapid recycling of glutamate transporters on the astroglial surface

1. Piotr Michaluk
2. Janosch Heller
3. Dmitri A. Rusakov

• Curated by eLife

  Summary: In this study, Michaluk et al. examined the membrane dynamics of the main glial glutamate transporter GLT1 in hippocampal astrocytes, which was previously shown to shape synaptic transmission through regulating extracellular levels of glutamate. Using GLT1 tagged on its surface with a pH-sensitive fluorescent marker, GLT1-SEP, the authors performed (1) fluorescence recovery after photobleaching (FRAP) experiments to assess the basal and activity-dependent dynamics of surface GLT1-SEP and (2) super-resolution dSTORM imaging to determine the relationship between GLT1 and PSD-95, an excitatory synapse marker. A large proportion of surface GLT1-SEP underwent turnover with a surface lifetime of 22 s, whereas a smaller fraction (~25%) remained largely immobile, which was decreased upon increased activity. Notably, the cytoplasmic domain of GLT1-SEP was shown to attenuate the basal turnover of surface GLT1 and to facilitate its proximal localization to synapses; moreover, GLT1 cytoplasmic domain was required for activity-dependent increase in the mobile fraction.

  While previous studies using single molecule tracking have demonstrated a role for the lateral diffusion of GLT1 in controlling the recruitment of GLT1 near active synapses, the present study uses powerful optical approaches and analysis tools to access both the surface lateral mobility and the exchange between surface and intracellular pools of GLT1. Furthermore, characterization of the nanoscale organization of GLT1 relative to synapses and its dependence on the C-terminal domain of GLT1 is presented. Altogether, the results are interesting and valuable, and underscore the importance of the GLT1 C-terminus in the membrane turnover and in the activity-dependent lateral diffusion of the surface GLT1. Nevertheless, some of the conclusions are not strongly supported by the data shown.

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

Reviewed by eLife

Inhibitory control of frontal metastability sets the temporal signature of cognition

1. Vincent Fontanier
2. Matthieu Sarazin
3. Frederic M Stoll
4. Bruno Delord
5. Emmanuel Procyk

• Curated by eLife

  Summary: Both reviewers found this study's findings to be interesting and novel, and they appreciated the integration of intrinsic timescale analysis, coding of behavioral signals, and exploration of mechanisms in a biophysical circuit model. However, they both raised serious concerns about methodological and interpretational aspects of the analyses which would need to be satisfactorily addressed in subsequent review. In consultation, both reviewers were in agreement with all points raised in the other's review. I view the two reviewers' requests and suggestions as appropriate and complementary, and all of them needed response.

  I highlight here two of the major concerns raised by the reviewers (but all raised by the reviewers merit addressing). First is the need for intrinsic timescale analysis to not be confounded by slowly varying changes in firing rate coding task variables (Point 1.2 of Reviewer 2). This is important for interpretation on intrinsic timescale and its correlation with task variable coding as a major result. Second is the interpretation and implementation of Hidden Markov Models to non-simultaneously recorded neurons (Points 6 of Reviewer 1 and 3 of Reviewer 2). Here again the HMM states may be driven by task variable coding which is not corrected for, which could confound interpretation of results as in terms of meta-stable states and its link to the circuit model. Furthermore, HMM analysis of the circuit model does not match its methodology for experimental data, but could be through non-simultaneous model spike trains, which the manuscript does not justify. I will add my own suggestion that perhaps both of these methodological data analysis concerns could potentially be addressed through comparison to the null model of a non-homogeneous Poisson process with firing rate given by the variable-coding PSTH. I do not consider it necessary to study a network model that performs the task, as suggested for consideration by Reviewer 1.

Reviewed by eLife