Neuroscience

AI-guided screen identifies probucol-mediated mitophagy enhancement through modulation of lipid droplets

1. Natalia Moskal
2. Naomi P. Visanji
3. Olena Gorbenko
4. Vijay Narasimhan
5. Hannah Tyrrell
6. Jess Nash
7. Peter N. Lewis
8. G. Angus McQuibban

Reviewed by Review Commons

The NAD+ precursor NMN activates dSarm to trigger axon degeneration in Drosophila

1. Arnau Llobet Rosell
2. Maria Paglione
3. Jonathan Gilley
4. Magdalena Kocia
5. Giulia Perillo
6. Massimiliano Gasparrini
7. Lucia Cialabrini
8. Nadia Raffaelli
9. Carlo Angeletti
10. Giuseppe Orsomando
11. Pei-Hsuan Wu
12. Michael P Coleman
13. Andrea Loreto
14. Lukas Jakob Neukomm

• Curated by eLife

  Evaluation Summary:

  Regulation of NAD and its intermediary metabolites is of critical importance in axon degeneration and in neurodegenerative disease. In mammals, the SARM1 NADase has been shown to be a metabolic sensor activated by an increase in the NMN/NAD+ ratio and SARM1 activation then leads to catastrophic energetic collapse and axon degeneration in disease and injury. This manuscript clarifies the role of NMN in activating the axon degeneration trigger dSARM in Drosophila. The authors analyze the signaling role of NMN, a NAD precursor metabolite involved in injury-induced axon degeneration, by overexpressing NMN-D, a prokaryotic enzyme that consumes NMN, using a stabilized version allowing for prolonged NMN depletion, and find that it is strongly protective in several in vivo injury paradigms in flies. This paper will be of interest to those in the neurodegeneration/axon injury field in general as an extensive set of optimized reagents is presented, confirming the crucial role of for exploring NAD-related axon degenerative pathways, and providing tools for neuroscientists to use Drosophila as a model for neurodegenerative research.

  (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

Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles

1. Julie M Sadino
2. Xander G Bradeen
3. Conor J Kelly
4. Liza E Brusman
5. Deena M Walker
6. Zoe R Donaldson

• Curated by eLife

  Evaluation Summary:

  This work will be of interest to behavioral neuroscientists with a focus on social behavior. The interrogation of the transcriptional signature of pair-bonding, in both short and long-term, is unique and made possible with the use of the monogamous vole. That there is a "degrading" of the transcriptome of pair bonding following separation is evident but there is a gap in understanding how the gene expression changes relate to behavior.

  (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.)

Reviewed by eLife

Stage-dependent differential influence of metabolic and structural networks on memory across Alzheimer’s disease continuum

1. Kok Pin Ng
2. Xing Qian
3. Kwun Kei Ng
4. Fang Ji
5. Pedro Rosa-Neto
6. Serge Gauthier
7. Nagaendran Kandiah
8. Juan Helen Zhou
9. Alzheimer's Disease Neuroimaging Initiative

• Curated by eLife

  Evaluation Summary:

  This work is of interest to neuroscientists and medical professionals involved in the study of Alzheimer's disease and related neurodegenerative conditions. The findings provide important information about how potential network-based structural and metabolic imaging biomarkers are associated with memory performance during distinct disease stages, in line with previous hypothetical biomarker models. The study is conceptually and methodologically sound, although some aspects of the analysis and reporting of the results could be further clarified.

  (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

Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability

1. Ian A Clark
2. Siawoosh Mohammadi
3. Martina F Callaghan
4. Eleanor A Maguire

• Curated by eLife

  Evaluation Summary:

  In this paper, the authors show that autobiographical memory recall is related to a specific biophysical property of the parahippocampal cingulum bundle, the so-called MR g-ratio. This paper will be of interest to neuroscientists studying associations between brain structure and cognitive processes. The data support the main conclusions of the paper. However, it is unclear how reliable the results are and whether the findings would generalize to situations beyond the specific one studied.

  (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

Phase separation of competing memories along the human hippocampal theta rhythm

1. Casper Kerrén
2. Sander van Bree
3. Benjamin J Griffiths
4. Maria Wimber

• Curated by eLife

  Evaluation Summary:

  This pre-registration study by Kerrén et al. used a proactive interference task in combination with MEG recordings on humans to test predictions of a previous computational model postulating that neural representations of competing memories are associated with varied phases of the hippocampus theta-band rhythm. Their results largely confirmed the hypothesis and suggest that reactivations of target and competitor memories indeed occur at different phases of theta oscillations, which is further related to the intrusion effect in behavior.

  (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

CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles

1. Brian D Mueller
2. Sean A Merrill
3. Shigeki Watanabe
4. Ping Liu
5. Longgang Niu
6. Anish Singh
7. Pablo Maldonado-Catala
8. Alex Cherry
9. Matthew S Rich
10. Malan Silva
11. Andres Villu Maricq
12. Zhao-Wen Wang
13. Erik M Jorgensen

• Curated by eLife

  Evaluation Summary:

  Using an elegant combination of cutting-edge techniques, the authors show that in the neuromuscular junction of the nematode C. elegans two different classes of voltage-activated calcium channels differentially trigger exocytosis of distinct pools of synaptic vesicles, one docked to the active zone and a second one localized more distant from the active zone. These findings will be of broad interest to neuroscientists interested in the mechanisms of calcium-mediated release of neurotransmitters at chemical synapses.

  (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.)

Reviewed by eLife

Multifunctional requirements for ERK1/2 signaling in the development of ganglionic eminence derived glia and cortical inhibitory neurons

1. Sara J. Knowles
2. Michael C. Holter
3. Guohui Li
4. George R. Bjorklund
5. Katherina P. Rees
6. Johan S. Martinez-Fuentes
7. Kenji J. Nishimura
8. Ariana E. Afshari
9. Noah Fry
10. April M Stafford
11. Daniel Vogt
12. Marco Mangone
13. Trent Anderson
14. Jason M. Newbern

• Curated by eLife

  eLife assessment

  This is an important study on the role of the Ras/MEK/Erk signaling cascade in brain development, with both theoretical and practical implications in multiple fields. The authors reveal functional redundancy and shared function for Erk1 and Erk2 in determining medial ganglionic eminence derived glial number, and exclude a role for Erk1 and Erk2 in the regulation of GABAergic neuron number or initial specification of GABAergic identity. They combine multiple methods including Ribotags, electrophysiology, and chemogenetic stimulation using DREADDs towards comprehensive conclusions. Reviewers expressed concerns about the coherence of the findings, and about the selection of controls mouse lines. Heterozygous ERK1/2 mice are used as 'het controls' throughout the manuscript, however, reviewers felt that there was not sufficient evidence that ERK levels in heterozygous mice are similar to wildtype mice. Nevertheless, these compelling findings will be of interest to a broad readership, and especially readers interested in kinase function and neurodevelopmental syndromes.

Reviewed by eLife

Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin-dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology

1. Anna Castano
2. Margaux Silvestre
3. Carrow I Wells
4. Jennifer L Sanderson
5. Carla A Ferrer
6. Han Wee Ong
7. Yi Lang
8. William Richardson
9. Josie A Silvaroli
10. Frances M Bashore
11. Jeffery L Smith
12. Isabelle M Genereux
13. Kelvin Dempster
14. David H Drewry
15. Navlot S Pabla
16. Alex N Bullock
17. Tim A Benke
18. Sila K Ultanir
19. Alison D Axtman

• Curated by eLife

  eLife assessment

  This important study reports selective CDKL5 inhibitors that may be of high interest to investigate the role of this kinase in disease (particularly, in CDKL5 deficiency disorder) and to address unsolved issues of inconsistency in the phenotypic characterization of CDKL5-deficient knockout mice. The evidence supporting the conclusions is convincing, with rigorous biochemical, in vitro and ex vivo assays. The work will be of interest to cell and medical biologists and epileptologists working in the fields of epilepsy and neural excitation.

Reviewed by eLife

History information emerges in the cortex during learning

1. Odeya Marmor
2. Yael Pollak
3. Chen Doron
4. Fritjof Helmchen
5. Ariel Gilad

• Curated by eLife

  eLife assessment

  This is important work analyzing the trial-by-trial progression of learning, and how the outcome of one trial influences cortex-wide neural responses on the next trial. However, the evidence for the central claims is incomplete because the potential confounds of slow hemodynamic effects and behavioral changes induced by the previous trial were not adequately addressed.

Reviewed by eLife