Neuroscience

Differential dopaminergic modulation of spontaneous cortico–subthalamic activity in Parkinson’s disease

1. Abhinav Sharma
2. Diego Vidaurre
3. Jan Vesper
4. Alfons Schnitzler
5. Esther Florin

• Curated by eLife

  Evaluation Summary:

  This manuscript is of broad interest to readers in the field of clinical neuroscience and movement disorders. The identification and characterization of dynamic networks that are differentially affected by dopaminergic medication in patients with Parkinson's disease is an important contribution to our understanding of physiologic and pathologic brain activities. The used methods provide the potential to uncover spectral, local, and temporal properties of dynamic neural systems. Overall, the data are properly analyzed, although many aspects of reporting the results could be worked out better.

  (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.)

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Psychomotor impairments and therapeutic implications revealed by a mutation associated with infantile Parkinsonism-Dystonia

1. Jenny I Aguilar
2. Mary Hongying Cheng
3. Josep Font
4. Alexandra C Schwartz
5. Kaitlyn Ledwitch
6. Amanda Duran
7. Samuel J Mabry
8. Andrea N Belovich
9. Yanqi Zhu
10. Angela M Carter
11. Lei Shi
12. Manju A Kurian
13. Cristina Fenollar-Ferrer
14. Jens Meiler
15. Renae Monique Ryan
16. Hassane S Mchaourab
17. Ivet Bahar
18. Heinrich JG Matthies
19. Aurelio Galli

• Curated by eLife

  Evaluation Summary:

  Infantile parkinsonism-dystonia is a rare but devastating condition that leads to early mortality. Mutations in the dopamine transporter that decrease its transport activity or cell surface expression have been identified as potential causes of this disease. Here, Aguilar et al perform a series of experiments to examine the effect of one of the mutations, R445C, on properties of the transporter in cell culture and on motor function in newly generated transgenic flies. They also explore structure function relationships of the mutation using X-ray crystallography of LeuT, a bacterial homolog, and molecular modeling. Lastly, they show blocking lysosomal degradation rescues a motor deficit in the flies. Insights from the work could lead to new approaches to specifically modulate the transporter structure to restore surface expression and function of the mutant dopamine transporter in this disorder. This elegant and technically sophisticated analysis is of interest to readers in the fields of neurobiology, behavior, and movement disorders, as the work provides an excellent example of using a variety of different approaches to determine the relationship between transporter structure and activity and potentially underlying pathology in human disease.

  (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

Evidence accumulation, not ‘self-control’, explains dorsolateral prefrontal activation during normative choice

1. Cendri A Hutcherson
2. Anita Tusche

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to neuroscientists studying decision-making and the frontal lobe. The paper combines computational modeling with brain imaging across several datasets to better understand the role of brain regions previously implicated in self-control during normative behavior (generosity, healthy eating). On balance, the data provide more support for the view that dorsolateral prefrontal cortex is involved in reading out the evidence in favor of different choice alternatives than the view that this region implements control processes that bias choices towards normative goals.

  (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.)

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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.)

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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.)

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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.)

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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