Neuroscience

Sensorimotor delays constrain robust locomotion in a 3D kinematic model of fly walking

1. Lili Karashchuk
2. Jing Shuang Li
3. Grant M Chou
4. Sarah Walling-Bell
5. Steven L Brunton
6. John C Tuthill
7. Bingni W Brunton

• Curated by eLife

  eLife Assessment

  This valuable study presents a computational model that simulates walking motions in Drosophila and suggests that, if sensorimotor delays in the neural circuitry were any longer, the system would be easily destabilized by external perturbations. The hierarchical control model is sensible and the evidence supporting the conclusions convincing. The modular model, which has many interacting components with varying degrees of biological realism, will serve as a well-grounded starting point for future studies that incorporate richer or more complete empirical data.

Reviewed by eLife

The geometry and dimensionality of brain-wide activity

1. Zezhen Wang
2. Weihao Mai
3. Yuming Chai
4. Kexin Qi
5. Hongtai Ren
6. Chen Shen
7. Shiwu Zhang
8. Guodong Tan
9. Yu Hu
10. Quan Wen

• Curated by eLife

  eLife Assessment

  This important study shows a surprising scale-invariance of the covariance spectrum of large-scale recordings in the zebrafish brain in vivo. A convincing analysis demonstrates that a Euclidean random matrix model of the covariance matrix recapitulates these properties. The results provide several new and insightful approaches for probing large-scale neural recordings.

Reviewed by eLife

An antisense oligonucleotide-based strategy to ameliorate cognitive dysfunction in the 22q11.2 Deletion Syndrome

1. Pratibha Thakur
2. Martin Lackinger
3. Anastasia Diamantopoulou
4. Sneha Rao
5. Yijing Chen
6. Khakima Khalizova
7. Annie Ferng
8. Curt Mazur
9. Holly Kordasiewicz
10. Robert J Shprintzen
11. Sander Markx
12. Bin Xu
13. Joseph A Gogos

• Curated by eLife

  eLife Assessment

  This is an important study that establishes how anti-sense oligonucleotides degrading a specific target protein called EMC10 can rescue neuronal function in models of chromosome 22.11.2 deletions. The authors use human iPSC-derived neurons and a mouse model to provide compelling data for the rescue of cellular and cognitive features of 22.11.2 phenotypes upon ASO regulation of EMC10. These pre-clinical data are of interest because they support reduction of ECM10 as a promising therapeutic strategy.

Reviewed by eLife

Activity-dependent synapse elimination requires caspase-3 activation

1. Zhou Yu
2. Andrian Gutu
3. Namsoo Kim
4. Erin K O'Shea

• Curated by eLife

  eLife Assessment

  This study presents an important finding on the involvement of a Caspase 3-dependent pathway in the elimination of synapses for retinogeniculate circuit refinement and eye-specific territory segregation. This work fits well with the concept of "synaptosis" which has been proposed in the past. The evidence supporting the claims of the authors is convincing, demonstrating that caspase-3 activation is essential for microglial elimination of synapses during both brain development and neurodegeneration. The work will be of interest to investigators studying cell death pathways, neurodevelopment, and neurodegenerative disease.

Reviewed by eLife

Progressively shifting patterns of co-modulation among premotor cortex neurons carry dynamically similar signals during action execution and observation

1. Zhonghao Zhao
2. Marc H Schieber

• Curated by eLife

  eLife Assessment

  This valuable study reports on the characteristics of premotor cortical population activity during the execution and observation of a moderately complex reaching and grasping task. By using new variants of well-established techniques to analyse neural population activity, the authors provide solid evidence that while the geometry of neural population activity changes between execution and observation, their dynamics are largely preserved. Although these findings are novel and robust, pending additional controls and analyses, the authors should further clarify the functional implications of their findings.

Reviewed by eLife

The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity

1. Andrew C Fleming
2. Nalini R Rao
3. Matthew Wright
4. Jeffrey N Savas
5. Evangelos Kiskinis

• Curated by eLife

  eLife Assessment

  Fleming et al sought to better understand DNAJC7's function in motor neurons as mutations in this gene have been associated with amyotrophic lateral sclerosis (ALS). Using iPSC-derived motor neurons, interactome, and transcriptomic data, they provide solid evidence that loss-of-function mutations in DNAJC7 disrupt RNA binding proteins and resistance to proteasomal stress. These important findings advance our understanding of DNAJC7 in motor neurons while providing clues to how its loss may be causal for ALS; nonetheless, the experiments were performed with a single iPSC line, while at least 3 are deemed to be required to validate the results. Furthermore, the mechanistic evidence is still incomplete with respect to how DNAJC7 mutations lead to HSF1 impaired activity, and whether it is direct or not.

Reviewed by eLife

Simply crushed zizyphi spinosi semen prevents neurodegenerative diseases and reverses age-related cognitive decline in mice

1. Tomohiro Umeda
2. Ayumi Sakai
3. Rumi Uekado
4. Keiko Shigemori
5. Ryota Nakajima
6. Kei Yamana
7. Takami Tomiyama

• Curated by eLife

  eLife assessment

  The authors made a useful finding that Zizyphi spinosi semen, a traditional Chinese medicine, has demonstrated excellent biological activity and potential therapeutic effects against Alzheimer's disease (AD). The researchers presented the effects, but the research evidence for the mechanism was incomplete. The main claims were only partially supported.

Reviewed by eLife

Enabling brain-wide mapping of layer-specific functional connectivity at 3T via layer-dependent fMRI with draining-vein suppression

1. Wei-Tang Chang
2. Weili Lin
3. Kelly S Giovanello

• Curated by eLife

  eLife Assessment

  This useful study presents a possible solution for a significant problem - that of draining vein sensitivity in functional MRI, which complicates the interpretability of laminar-fMRI results. The addition of a low diffusion-weighted gradient is presented to remove the draining vein signal and obtain functional responses with higher spatial fidelity. However, the strength of the evidence is incomplete, and most tests appear to have been done only in a single subject. Significance thresholds in presented maps are very low and most cortical depth-dependent response profiles do not differ from baseline, even in the BOLD data shown as reference. Curiously, even BOLD group data fails to replicate the well-known pattern of draining towards the cortical surface.

Reviewed by eLife

Effects of nicotine compared to placebo gum on sensitivity to pain and mediating effects of peak alpha frequency

1. Samantha K Millard
2. Alan KI Chiang
3. Peter Humburg
4. Nahian Chowdhury
5. Raafay Rehan
6. Andrew J Furman
7. Ali Mazaheri
8. Siobhan M Schabrun
9. David A Seminowicz

• Curated by eLife

  eLife Assessment

  In this useful study, Millard et al. assessed the effects of nicotine on pain sensitivity and peak alpha frequency (PAF). The evidence shown is incomplete to support the key claim that nicotine modulates PAF or pain sensitivity, considering the effect sizes observed. This raises the question of whether the chosen experimental intervention was the most suitable approach for investigating their research question. Nonetheless, the work can be incorporated into the literature investigating the relationship between nicotine and pain, and could be of broad interest to pain researchers.

Reviewed by eLife

Mitochondrial dysfunction heightens the integrated stress response to drive ALS pathogenesis

1. Curran Landry
2. James Costanzo
3. Miguel Mitne-Neto
4. Mayana Zatz
5. Ashleigh Schaffer
6. Maria Hatzoglou
7. Alysson Muotri
8. Helen Cristina Miranda

Reviewed by Review Commons