Neuroscience

Cholinergic signalling in the forebrain controls microglial phenotype and responses to systemic inflammation

1. Arshed Nazmi
2. Eadaoin W. Griffin
3. Robert H. Field
4. Sean Doyle
5. Edel Hennessy
6. Martin O’Donnell
7. Aisling Rehill
8. Anthony McCarthy
9. Daire Healy
10. Michelle M. Doran
11. John P. Lowry
12. Colm Cunningham

• Curated by eLife

  Evaluation Summary:

  Loss or decrease of cholinergic tone occurs during brain aging or in pathologies such as Alzheimer's disease. This elegant study has used in vitro and in vivo approaches to explore the impact of decreased cholinergic signaling on hippocampal/cortical microglial state. The study demonstrates that the neurotransmitter Acetylcholine (ACh) maintain microglial cells in a homeostatic state, preventing their priming towards an activated state that leads to an exacerbated response to an inflammatory stimulus. The study thus provides important insights on the feed-forward contribution of microglial cells to neurodegenerative conditions.

  (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

Early life experience sets hard limits on motor learning as evidenced from artificial arm use

1. Roni O Maimon-Mor
2. Hunter R Schone
3. David Henderson Slater
4. A Aldo Faisal
5. Tamar R Makin

• Curated by eLife

  Evaluation Summary:

  This is a large study of the development of human sensorimotor control using unique populations who have undergone limb loss at different times in their lives.This paper will be of interest to scientists within the field of motor control and for those interested in the development and plasticity of the motor system. An important finding is that reaching performance with an artificial arm is better in people who lost their limb in adulthood and worse in those with congenital limb loss. While the mechanisms underlying this result are not yet clear, it suggests that the benefits of early developmental experience with an intact limb are superior to early experience with an artificial arm.

  (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

Differential conditioning produces merged long-term memory in Drosophila

1. Bohan Zhao
2. Jiameng Sun
3. Qian Li
4. Yi Zhong

• Curated by eLife

  Evaluation Summary:

  This work reveals a novel form of Drosophila long-term memory (LTM) that is of potential interest to most neuroscientists working on various animals. While classical protein-synthesis-dependent LTM forms only after repetitive spaced trials of olfactory conditioning, the authors discovered that flies also form a "blurred" or "vague" protein-synthesis-dependent LTM which distinguishes the experienced two odors from the third naive odor after single-trial training. This merged LTM lacking the event details likely occurs in most animals since long-lasting memory of occasional threatening experiences for future escape behavior is crucial for survival.

  (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

Diversity of excitatory release sites

1. Maria Rita Karlocai
2. Judit Heredi
3. Tünde Benedek
4. Noemi Holderith
5. Andrea Lorincz
6. Zoltan Nusser

• Curated by eLife

  Evaluation Summary:

  The authors study how individual synapses can compute information by tuning the properties of the individual components that drive synaptic communication between neurons. Using cutting edge physiology and morphology they show that the reliability of synaptic communication depends not only on how many units drive synaptic communication, but also the authors suggest that individual units vary in their quantitative molecular composition.

  (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

The Nt17 domain and its helical conformation regulate the aggregation, cellular properties and neurotoxicity of mutant huntingtin exon 1

1. Sophie Vieweg
2. Anne-Laure Mahul-Mellier
3. Francesco S. Ruggeri
4. Nathan Riguet
5. Sean M. DeGuire
6. Anass Chiki
7. Urszula Cendrowska
8. Giovanni Dietler
9. Hilal A. Lashuel

Reviewed by Review Commons

7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome

1. Hideaki Tomita
2. Kelly M Hines
3. Josi M Herron
4. Amy Li
5. David W Baggett
6. Libin Xu

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to developmental biologists and neuroscientists as it aims to resolve the unknown mechanism by which loss of a key enzyme in cholesterol biosynthesis results in neurodevelopmental defects. It provides a conceptual framework for understanding how altered lipid metabolism can impact brain development. Many of the key claims of the paper are well-supported, but reasonable alternative explanations remain.

  (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

Sustained expression of unc-4 homeobox gene and unc-37/Groucho in postmitotic neurons specifies the spatial organization of the cholinergic synapses in C. elegans

1. Mizuki Kurashina
2. Jane Wang
3. Jeffrey Lin
4. Kathy Kyungeun Lee
5. Arpun Johal
6. Kota Mizumoto

• Curated by eLife

  Evaluation Summary:

  This paper is of potential interest to a broad audience of neuroscientists, as it adds to our growing understanding of transcriptional mechanisms that regulate neural connectivity. Specifically, the paper provides support for the idea that transcriptional pathways previously implicated in neuronal cell fate determination can have independent roles in specifying connectivity between neurons. The study is highly technically innovative and cleverly uses a set of newly developed tools to analyze the developmental time window over which transcriptional activity is required to achieve to proper connectivity. However, the paper falls a little short in defining specific mechanisms involved downstream of the transcription factors themselves.

  (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

Single-cell analysis of the ventricular-subventricular zone reveals signatures of dorsal and ventral adult neurogenesis

1. Arantxa Cebrian-Silla
2. Marcos Assis Nascimento
3. Stephanie A Redmond
4. Benjamin Mansky
5. David Wu
6. Kirsten Obernier
7. Ricardo Romero Rodriguez
8. Susana Gonzalez-Granero
9. Jose Manuel García-Verdugo
10. Daniel A Lim
11. Arturo Álvarez-Buylla

• Curated by eLife

  Evaluation Summary:

  Redmond et al. use single-cell and single-nucleus RNA-sequencing to reveal the molecular heterogeneity that underlies regional differences in neural stem cells in the adult mouse. Prior work had separate subventricular stem cells as type A and B. By generating bulk and single cell transcriptome sequence data, the authors identified a distinct subtype of both A and B cells that differentiate into dorsal and ventral identities. They also identify a set of genes that constitute a conserved molecular signature of these cell types.

  (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

GluA4 enables associative memory formation by facilitating cerebellar expansion coding

1. Katarzyna Kita
2. Catarina Albergaria
3. Ana S. Machado
4. Megan R. Carey
5. Martin Müller
6. Igor Delvendahl

• Curated by eLife

  Evaluation Summary:

  This work explores the cellular and behavioural effects of a genetically induced reduction of the expression of a glutamate (excitatory) receptor (GluA4), focusing on the cerebellum , a structure involved in the acquisition of arbitrary, complex motor reflexes. The authors show that synaptic transmission at the input layer to the cerebellar cortex is reduced, despite some compensation by other mechanisms, which are characterised. Locomotion is little affected while acquisition of a "conditioned eyeblink" is abolished. The authors try to link the cellular and behavioural phenomena via modelling of the cerebellar computation, although this is not definitive. The work is of high quality, of interest to cerebellar physicists and neurocomputational modellers in particular.

  (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

Optical analysis of the action range of glutamate in the neuropil

1. E.A. Matthews
2. W. Sun
3. S.M. McMahon
4. M. Doengi
5. L. Halka
6. S. Anders
7. J.A. Müller
8. P. Steinlein
9. N. Vana
10. G. van Dyk
11. J. Pitsch
12. A.J. Becker
13. A. Pfeifer
14. E.T. Kavalali
15. A. Lamprecht
16. C. Henneberger
17. V. Stein
18. S. Schoch
19. D. Dietrich

• Curated by eLife

  Evaluation Summary:

  The authors address the spatial spread of glutamate outside of synapses, with the surprising conclusion that glutamate released at one synapse can strongly activate receptors at neighboring synapses. This manuscript should interest those studying neural signaling and techniques associated with that field. However, caveats of the advanced techniques used to address this difficult question limit the strength of the main conclusion.

  (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