Neuroscience

A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels

1. Yucheng Xiao
2. Jonathan W Theile
3. Agnes Zybura
4. Yanling Pan
5. Zhixin Lin
6. Theodore R Cummins

• Curated by eLife

  eLife assessment

  This is an exciting and important study that constitutes a major advance in the molecular understanding of resurgent Na current. Reproducing resurgent current by expression of two proteins has never been done. Here, the authors have for the first time molecularly reconstituted Na channels that produce resurgent Na current. Not only do these experiments satisfactorily and convincingly address a long-standing question in the field, but they also open the door to molecular manipulation of this current, potentially of significant practical use given the proposed role of the current in several disorders and disease states, including pain. The work will be of interest to many neuroscientists.

Reviewed by eLife

Time-resolved parameterization of aperiodic and periodic brain activity

1. Luc Edward Wilson
2. Jason da Silva Castanheira
3. Sylvain Baillet

• Curated by eLife

  Evaluation Summary:

  The paper addresses the highly timely questions of how to quantify aperiodic and periodic neural activity. This was done by extending previous work by embracing time-resolved parametrization of both simulated, noninvasive EEG and intracranial data. The new approach is termed Spectral Parametrization Resolved in Time (SPRiNT) and the paper shows that the slope of aperiodic activity is linked with both behaviour and age. The method thus demonstrates the importance of evaluating the state-dependence of aperiodic activity and dynamic properties of oscillatory components in a time-resolved manner.

  (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 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Allosteric stabilization of calcium and phosphoinositide dual binding engages several synaptotagmins in fast exocytosis

1. Janus RL Kobbersmed
2. Manon MM Berns
3. Susanne Ditlevsen
4. Jakob B Sørensen
5. Alexander M Walter

• Curated by eLife

  Evaluation Summary:

  Synaptotagmins are Ca2+ sensors for synchronous neurotransmitter release. However, despite intense study it remains unclear exactly how the binding of 5 Ca2+ ions to Synaptotagmin's two C2 domains leads to the observed Ca2+ dependence of vesicle fusion. This study puts forward a novel mechanistic model of neurotransmitter vesicle fusion (vesicle exocytosis) which is relatively simple but significantly more detailed than the widely used phenomenological models of calcium-dependent fast exocytosis.

  (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

State-dependent activity dynamics of hypothalamic stress effector neurons

1. Aoi Ichiyama
2. Samuel Mestern
3. Gabriel B Benigno
4. Kaela E Scott
5. Brian L Allman
6. Lyle Muller
7. Wataru Inoue

• Curated by eLife

  Evaluation Summary:

  The observations from high quality in vivo and in vitro recordings of tagged CHR neurons are supported by a computational model that suggests feedback inhibition may regulate the activity patterns of CRH neurons in distinct states, and represent an important contribution. The authors also present an unexpected observation that uncovers interesting neural dynamics that will provide the impetus for new studies exploring firing characteristics in discrete physiological and emotional states. Previous work reaching an opposite conclusion and likely effects of urethane on in vivo recordings are not discussed.

  (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 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Botulinum neurotoxin accurately separates tonic vs. phasic transmission and reveals heterosynaptic plasticity rules in Drosophila

1. Yifu Han
2. Chun Chien
3. Pragya Goel
4. Kaikai He
5. Cristian Pinales
6. Christopher Buser
7. Dion Dickman

• Curated by eLife

  Evaluation Summary:

  The authors describe a new tool to completely block both evoked and spontaneous release in a selective manner using the GAL4 system in Drosophila. Surprisingly, they see no effects on either pre or postsynaptic development when both evoked and spontaneous release are blocked, in contrast to prior studies in the field. Overall, the results are provocative and will be of interest to the field. The study contradicts a number of published works, so it is important for the field to see the data and be able to evaluate it 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. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Higher-order olfactory neurons in the lateral horn support odor valence and odor identity coding in Drosophila

1. Sudeshna Das Chakraborty
2. Hetan Chang
3. Bill S Hansson
4. Silke Sachse

• Curated by eLife

  Evaluation Summary:

  Information about the environment obtained through sensory organs is processed and utilized at multiple levels in the brain. In this study, the authors use a variety of modern genetic and optophysiological tools to uncover the function and connectivity of glutamatergic neurons in a higher brain center of Drosophila - the lateral horn. They find that these neurons do not only encode chemical odor identity, but also the hedonic value (attractive or repulsive) of odors. This advances our understanding of how odors are represented in the brain will be of value to those who are interested in odour coding and behavioural valence of various odours.

  (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 name with the authors.)

Reviewed by eLife

Early detection of cerebrovascular pathology and protective antiviral immunity by MRI

1. Li Liu
2. Steve Dodd
3. Ryan D Hunt
4. Nikorn Pothayee
5. Tatjana Atanasijevic
6. Nadia Bouraoud
7. Dragan Maric
8. E Ashley Moseman
9. Selamawit Gossa
10. Dorian B McGavern
11. Alan P Koretsky

• Curated by eLife

  Evaluation Summary:

  The manuscript by Liu et al., aims to develop a novel MRI-based approach to monitor virus specific CD8+ T cells and their relationship to cerebrovascular pathology in living brains. Using a mouse model of VSV brain infection, they show that MRI approaches can be used to identify microbleeds in the brain, and these microbleeds occur independent of immune cell influx. Furthermore, the transfer of low numbers of virus specific CD8+ T cells can reduce cerebrovascular bleeding. The capacity to track virus specific T cells and cerebrovascular pathology in real time in living brains would be a major technological advance.

  (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

Modified viral-genetic mapping reveals local and global connectivity relationships of ventral tegmental area dopamine cells

1. Kevin Beier

• Curated by eLife

  Evaluation Summary:

  By addressing shortcomings in rabies viral-mediated labeling of monosynaptic inputs to ventral tegmental area dopamine neurons, this study provides a previously unattained precision local inputs to VTA dopamine neurons. Main findings include the preservation of a medial to lateral topography in the projection patterns within VTA microcircuitry, prominence of inhibition of DA neurons from the substantial nigra pars reticulata (SNr), DA-DA transmission, and inputs from raphe serotonin neurons. The precise local VTA connectivity described here is important for identifying how dopamine neurons compute reward, prediction, and movement-related signals during behavior, and thus is likely to be of interest to neuroscientists interest in those processes and the midbrain dopamine system.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Imaging of the pial arterial vasculature of the human brain in vivo using high-resolution 7T time-of-flight angiography

1. Saskia Bollmann
2. Hendrik Mattern
3. Michaël Bernier
4. Simon D Robinson
5. Daniel Park
6. Oliver Speck
7. Jonathan R Polimeni

• Curated by eLife

  Evaluation Summary:

  This article revisits a classical magnetic resonance imaging technique to image the brain's vasculature, showing that small blood vessels, deemed too difficult to image, could be targeted effectively with extremely high resolution imaging. This proof-of-concept, both theoretical and experimental, may be of use to build detailed models of brain physiology and detect fine alterations of the vessels in 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Repeated ethanol exposure and withdrawal alters angiotensin‐converting enzyme 2 expression in discrete brain regions: Implications for SARS‐CoV ‐2 neuroinvasion

1. Nagalakshmi Balasubramanian
2. Thomas D. James
3. Govindhasamy Pushpavathi Selvakumar
4. Jessica Reinhardt
5. Catherine A. Marcinkiewcz

Reviewed by ScreenIT