Neuroscience

Establishment of transgenic fluorescent mice for labeling synapses and screening synaptogenic adhesion molecules

1. Lei Yang
2. Jingtao Zhang
3. Sen Liu
4. Yanning Zhang
5. Li Wang
6. Xiaotong Wang
7. Shanshan Wang
8. Ke Li
9. Mengping Wei
10. Chen Zhang

• Curated by eLife

  eLife assessment

  The fluorescently tagged SYT-1 mouse line will be useful for the field. Importantly, the authors used a comprehensive set of immunohistochemical and physiological experiments to demonstrate that the fluorescence tagging did not alter the function of SYT-1. These are important control experiments that will make the strain useful for physiological experiments in the future. However, the advance of this manuscript is less clear.

Reviewed by eLife

Obesogenic diet induces circuit-specific memory deficits in mice

1. Ioannis Bakoyiannis
2. Eva Gunnel Ducourneau
3. Mateo N'diaye
4. Alice Fermigier
5. Celine Ducroix-Crepy
6. Clementine Bosch-Bouju
7. Etienne Coutureau
8. Pierre Trifilieff
9. Guillaume Ferreira

• Curated by eLife

  Evaluation Summary:

  This work is valuable for those who study how diet and metabolism impact neurological function, specifically learning and memory since it investigates the impact of high-fat diet intake during the preadolescent period on memory performances. The data convincingly showed the possibility to reverse memory deficits related to obesity by manipulating selected hippocampal circuits. The claims would benefit from additional controls and analyses.

  (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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The Na+ leak channel NALCN controls spontaneous activity and mediates synaptic modulation by α2-adrenergic receptors in auditory neurons

1. Tenzin Ngodup
2. Tomohiko Irie
3. Seán P Elkins
4. Laurence O Trussell

• Curated by eLife

  eLife assessment

  This paper reports the fundamental discovery of adrenergic modulation of spontaneous firing through the inhibition of the Na+ leak channel NALCN in cartwheel cells in the dorsal cochlear nucleus. This study provides unequivocal evidence that the activation of alpha-2 adrenergic or GABA-B receptors inhibit NALCN currents to reduce neuronal excitability. The evidence supporting the conclusions is exceptional, the electrophysiological data is high quality and the experimental design is rigorous.

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Toolkits for detailed and high-throughput interrogation of synapses in C. elegans

1. Maryam Majeed
2. Haejun Han
3. Keren Zhang
4. Wen Xi Cao
5. Chien-Po Liao
6. Oliver Hobert
7. Hang Lu

• Curated by eLife

  eLife assessment

  Studies of synaptic development and plasticity in the nematode C. elegans have been limited by the difficulty of rapid, accurate assessments of synaptic structure. Here, with a series of convincing studies, the authors introduce and validate a valuable computational pipeline, "WormPsyQi," that allows rapid, reproducible quantitation of fluorescent synaptic puncta while minimizing human error and bias. The authors also describe a new set of strains carrying synaptic markers. Together, these tools should provide groups studying this model system with the ability to quantitatively characterize chemical and electrical synapses, even in densely packed regions in 3D space such as the nerve ring.

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Drift of neural ensembles driven by slow fluctuations of intrinsic excitability

1. Geoffroy Delamare
2. Yosif Zaki
3. Denise J Cai
4. Claudia Clopath

• Curated by eLife

  eLife assessment

  This is an important theoretical study providing insight into how fluctuations in excitability can contribute to gradual changes in the mapping between population activity and stimulus, commonly referred to as representational drift. The authors provide convincing evidence that fluctuations can contribute to drift. Overall, this is a well-presented study that explores the question of how changes in intrinsic excitability can influence distinct memory representations.

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Changes in lipid metabolism track with the progression of neurofibrillary pathology in tauopathies

1. Dominika Olešová
2. Dana Dobešová
3. Petra Majerová
4. Radana Brumarová
5. Aleš Kvasnička
6. Štěpán Kouřil
7. Eva Stevens
8. Jozef Hanes
9. Ľubica Fialová
10. Alena Michalicová
11. Juraj Piešťanský
12. Jakub Šinský
13. Petr Kaňovský
14. David Friedecký
15. Andrej Kováč

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Microglia facilitate and stabilize the response to general anesthesia via modulating the neuronal network in a brain region-specific manner

1. Yang He
2. Taohui Liu
3. Quansheng He
4. Wei Ke
5. Xiaoyu Li
6. Jinjin Du
7. Suixin Deng
8. Zhenfeng Shu
9. Jialin Wu
10. Baozhi Yang
11. Yuqing Wang
12. Ying Mao
13. Yanxia Rao
14. Yousheng Shu
15. Bo Peng

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on the mechanisms underlying general anesthesia, with a focus on microglial regulation. The evidence supporting the claims of the authors is solid, although some of the novelty of these findings may be reduced based on the recent publication of a similar study. The work will be of interest to medical biologists working on mechanisms of anesthesia, microglia, and neuron-microglia interaction.

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Supercomputer framework for reverse engineering firing patterns of neuron populations to identify their synaptic inputs

1. Matthieu K Chardon
2. Y Curtis Wang
3. Marta Garcia
4. Emre Besler
5. J Andrew Beauchamp
6. Michael D'Mello
7. Randall K Powers
8. Charles J Heckman

• Curated by eLife

  eLife assessment

  The study by Chardon et al. is fundamental to advancing our understanding of presynaptic control of motor neuron output. Large-scale computer simulations were performed using well-established single motor neuron models to provide compelling evidence regarding the time-varying patterns of inputs that control motor neuron ensembles. The work will interest the community of motor control, motor unit physiology, neural engineering, and computational neuroscience.

Reviewed by eLife

A maximum of two readily releasable vesicles per docking site at a cerebellar single active zone synapse

1. Melissa Silva
2. Van Tran
3. Alain Marty

• Curated by eLife

  eLife assessment

  The study used slice physiology and modeling to investigate neurotransmitter release at the cerebellar parallel fiber-to-molecular layer interneuron synapse, revealing that each docking site can accommodate up to two synaptic vesicles simultaneously. The evidence presented is convincing. These important findings validate a two-step docking model and shed light on the mechanisms underlying short-term synaptic plasticity and strategies for achieving synaptic reliability, which plays a critical role in information processing in the brain.

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Balance of activity during a critical period tunes a developing network

1. Iain Hunter
2. Bramwell Coulson
3. Tom Pettini
4. Jacob J Davies
5. Jill Parkin
6. Matthias Landgraf
7. Richard A Baines

• Curated by eLife

  eLife assessment

  This valuable study combines electrophysiology and neuroanatomy with pharmacological and optogenetic manipulation in the Drosophila genetic model system to pinpoint the neural substrate that is influenced by altered activity during a critical period (CP) of larval locomotor circuit development. Increasing activity during the CP causes permanent network changes, manifesting in increased recovery times from seizures and altered intersegmental coordination during locomotion, thus indicating that a setpoint of network excitability is determined during the CP. Next, compelling experiments demonstrate that this goes along with increased excitation/inhibition ratios to single identified motoneurons and most importantly, for excitability setpoint determination during the CP excitatory and inhibitory inputs are integrated such that the effect of CP hyperexcitation is rescued by the stimulation of endogenous inhibitory inputs to the motoneurons. This provides novel insight into how developing neural network excitability is tuned and how it can be entrained during the CP.

Reviewed by eLife