Neuroscience

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

Decoding the hidden variabilities in mPFC descending pathways across emotional states

1. Chien-Hsien Lai
2. Gyeongah Park
3. Pan Xu
4. Xiaoqian Sun
5. Qian Ge
6. Zhen Jin
7. Sarah Betts
8. Xiaojie Liu
9. Qingsong Liu
10. Rahul Simha
11. Chen Zeng
12. Hui Lu
13. Jianyang Du

• Curated by eLife

  eLife Assessment

  Du et al. present a valuable study on neural activation in medial prefrontal cortex (mPFC) subpopulations projecting to the basolateral amygdala (BLA) and nucleus accumbens (NAc) during behavioral tasks assessing anxiety, social preference, and social dominance. The study has innovative approaches and solid in vivo calcium imaging data, but the evidence linking neural physiology to behavioral outcomes is incomplete. Addressing these gaps would significantly enhance the understanding of how distinct mPFC→BLA and mPFC→NAc pathways influence anxiety, exploration, and social behaviors.

Reviewed by eLife

Mapping serotonergic dynamics using drug-modulated molecular connectivity in rats

1. Tudor M Ionescu
2. Mario Amend
3. Rakibul Hafiz
4. Andreas Maurer
5. Bharat Biswal
6. Hans F Wehrl
7. Kristina Herfert

• Curated by eLife

  eLife Assessment

  This important paper on measuring molecular connectivity using combined serotonin PET and resting-state fMRI provides both novel methods for studying the brain as well as insights into the effects of ecstasy administration. The methods are convincing, with the high anaesthetic dose used likely limiting network activity.

Reviewed by eLife

A general framework for characterizing optimal communication in brain networks

1. Kayson Fakhar
2. Fatemeh Hadaeghi
3. Caio Seguin
4. Shrey Dixit
5. Arnaud Messé
6. Gorka Zamora-López
7. Bratislav Misic
8. Claus C Hilgetag

• Curated by eLife

  eLife Assessment

  The authors provide a compelling method for characterizing communication within brain networks. The study engages important, biologically pertinent, concerns related to the balance of dynamics and structure in assessing the focal points of brain communication. It will be of interest to researchers trying to dissect structure of complex interaction networks across scales, from cells to regions.

Reviewed by eLife

Axonal injury signaling is restrained by a spared synaptic branch

1. Laura J Smithson
2. Juliana Zang
3. Lucas Junginger
4. Thomas J Waller
5. Reilly Jankowiak
6. Sophia Khan
7. Ye Li
8. Dawen Cai
9. Catherine A Collins

• Curated by eLife

  eLife Assessment

  This important study leverages the power of Drosophila genetics and sparsely-labeled neurons to propose an intriguing new model for neuronal injury signaling. The authors present convincing evidence to show that the somatic response to axonal injury can be suppressed if the injury is not complete, suggesting the presence of a new mode of injury 'integration.' While the underlying mechanism of this fascinating observation has yet to be determined, the phenomenon itself will be of broad significance in the field.

Reviewed by eLife

Dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons

1. Giulia Di Bartolomei
2. Raul Ortiz
3. Dietmar Schreiner
4. Susanne Falkner
5. Esther E Creemers
6. Peter Scheiffele

• Curated by eLife

  eLife Assessment

  This study reports that the RNA binding and cardiomyopathy-associated protein RBM20 is expressed in specific populations of neurons in the CNS, where it binds to and regulates the expression of synapse-related RNAs. This is an important finding because it reveals a new mechanism for gene regulation in neurons by an RNA binding protein previously studied in the heart; the authors also provide data to suggest that the mechanism by which RBM20 acts in neurons may be distinct from the splicing regulation studied in cardiac tissue. The data in support of the binding and regulation of RNAs by RBM20 is compelling, using leading edge sequencing methods to determine RNA binding profiles, and cell type specific genetics for evaluation of function.

Reviewed by eLife