Neuroscience

Behavioral control by depolarized and hyperpolarized states of an integrating neuron

1. Aylesse Sordillo
2. Cornelia I Bargmann

• Curated by eLife

  Evaluation Summary:

  The interneuron RIM affects many behaviours in C. elegans. Attempts to understand or manipulate its function have sometimes led to conflicting and difficult to interpret results. Sordillo and Bargmann investigate the role of the RIM in locomotion by manipulating it's signaling properties in multiple ways. The strength of this approach is that targeting multiple biological signaling mechanisms, they are able to conduct a nuanced analysis of RIM's signaling functions that goes beyond simplistic ON/OFF distinctions. They reach two primary conclusions: 1. RIM depolarization extends reversals via synaptic (glutamatergic) and secretory (tyraminergic) signaling; 2. RIM hyperpolarization promotes forward locomotion via electrical signaling through gap junctions. As a result, RIM was shown to act for stabilizing both forward and backward movement, which is important for understanding of C. elegans in general. Also, the implication that interneurons can be multifunctional in this way is intriguing and potentially impactful.

  (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

Identification of a stereotypic molecular arrangement of endogenous glycine receptors at spinal cord synapses

1. Stephanie A Maynard
2. Philippe Rostaing
3. Natascha Schaefer
4. Olivier Gemin
5. Adrien Candat
6. Andréa Dumoulin
7. Carmen Villmann
8. Antoine Triller
9. Christian G Specht

Reviewed by Review Commons

Suppression weakens unwanted memories via a sustained reduction of neural reactivation

1. Ann-Kristin Meyer
2. Roland G Benoit

• Curated by eLife

  Evaluation Summary:

  The goal of this study was to test whether multiple attempts at suppressing the retrieval of an (emotional) memory is associated with degradation of the representation of information in the brain about such memories. A combination of sophisticated computational modelling in fMRI reveals that neural representations of previously suppressed memories are sustainably weakened during memory retrieval attempts. This manuscript is of interest for neuroscientists in the field of motivated forgetting and memory control.

  (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

Presynaptic stochasticity improves energy efficiency and helps alleviate the stability-plasticity dilemma

1. Simon Schug
2. Frederik Benzing
3. Angelika Steger

• Curated by eLife

  Evaluation Summary:

  In large nervous systems such as mammalian cortex excitatory synapses are stochastic and the probability of release of neurotransmitter can be modulated by plasticity and neural activity. This paper presents a simple biologically plausible mechanism that regulates the probability of release during learning. Using network simulations the authors show that this can result in more energy efficient processing of learned stimuli by enhancing the reliability of important connections, with lower expected rates of transmission at less important 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 #2 agreed to share their name with the authors.

Reviewed by eLife

Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models of HCN1 epileptic encephalopathy

1. Andrea Merseburg
2. Jacquelin Kasemir
3. Eric W Buss
4. Felix Leroy
5. Tobias Bock
6. Alessandro Porro
7. Anastasia Barnett
8. Simon E Tröder
9. Birgit Engeland
10. Malte Stockebrand
11. Anna Moroni
12. Steven A Siegelbaum
13. Dirk Isbrandt
14. Bina Santoro

• Curated by eLife

  Evaluation Summary:

  This is an innovative and important paper with interest to basic and translational neuroscientists that demonstrates the power of experimental models to advance our understanding of human disease. The authors focus on early-life epilepsy, a devastating and common disorder, and specifically on genetic epilepsies generated via pathological sequence variations in the hyperpolarization-activated nonspecific cation (HCN) channel subtype 1. They delineate the epileptic phenotype and demonstrate some of the potential mechanisms leading to the generation of spontaneous seizures in genetically engineered mice.

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

Reviewed by eLife

Parallel processing in speech perception with local and global representations of linguistic context

1. Christian Brodbeck
2. Shohini Bhattasali
3. Aura AL Cruz Heredia
4. Philip Resnik
5. Jonathan Z Simon
6. Ellen Lau

• Curated by eLife

  Evaluation Summary:

  Brodbeck and colleagues make a strong contribution to the field of neurolinguistics by asking whether speech comprehension uses local (e.g., sublexical) or global (e.g., sentences) contextual probabilities. To tackle this, they recorded participants with magnetoencephalography while they listened to a story. The authors assessed which of three possible speech models best explained brain activity using state-of-the-art analyses and information-theoretic measures. The authors report strong and valuable evidence for both local and global contextual analyses supporting the coexistence of both hierarchical and parallel speech processing in the human brain.

  (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

All-trans retinoic acid induces synaptopodin-dependent metaplasticity in mouse dentate granule cells

1. Maximilian Lenz
2. Amelie Eichler
3. Pia Kruse
4. Julia Muellerleile
5. Thomas Deller
6. Peter Jedlicka
7. Andreas Vlachos

• Curated by eLife

  Evaluation Summary:

  All-trans retinoic acid (atRA) is a potent regulator of synaptic function known to be critical for certain forms of homeostatic plasticity. Previous work by the Vlachos group established that atRA also modulates synaptic function in human cortex and linked the synaptic effects of atRA to the spine apparatus protein synaptopodin. As a follow up study, the present work investigated the effect of atRA in the hippocampus. The authors found that atRA can play a key role in modulating enduring forms of synaptic plasticity in the dentate gyrus of the hippocampus even when it does not seem to drive overt changes in basal synaptic function, and this "metaplasticity"-related effects also require synaptopodin. Together, these studies establish a critical role of atRA in modulating synaptic transmission and plasticity at multiple regions of the human brain.

  (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

Disturbed retinoid metabolism upon loss of rlbp1a impairs cone function and leads to subretinal lipid deposits and photoreceptor degeneration in the zebrafish retina

1. Domino K Schlegel
2. Srinivasagan Ramkumar
3. Johannes von Lintig
4. Stephan CF Neuhauss

• Curated by eLife

  Evaluation Summary:

  In mammals the cellular retinaldehyde binding protein, CRALBP, is expressed in the pigment epithelium (RPE) and in Müller glial cells (MGCs) in the retina. Zebrafish has two copies of the gene, each expressed in one of the cell types. By knocking out each gene with CRISPR/Cas9, the authors could show that it is the copy expressed in the RPE that is essential for turnover of retinal and for cone function. Thus, the zebrafish gene duplication suggests that the RPE role of CRALBP is the important one also in humans, implying the RPE as target for future gene therapy in humans with mutations in CRALBP.

  (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.)

Reviewed by eLife

Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum

1. Alex Reichenbach
2. Rachel E Clarke
3. Romana Stark
4. Sarah Haas Lockie
5. Mathieu Mequinion
6. Harry Dempsey
7. Sasha Rawlinson
8. Felicia Reed
9. Tara Sepehrizadeh
10. Michael DeVeer
11. Astrid C Munder
12. Juan Nunez-Iglesias
13. David C Spanswick
14. Randall Mynatt
15. Alexxai V Kravitz
16. Christopher V Dayas
17. Robyn Brown
18. Zane B Andrews

• Curated by eLife

  Evaluation Summary:

  The authors demonstrate that selective inactivation of carnitine acetyltransferase (Crat) – a key metabolic enzyme – in AgRP neurons attenuates the response of AgRP neurons to peanut butter (PB) chips, the release of dopamine in the nucleus accumbens, and the motivation to work for food when mice are fasted. The strength of this study is the demonstration that metabolic sensing by AgRP neurons is somehow linked to dopamine release in the nucleus accumbens, but a weakness is that it is unclear how the lack of Crat in AgRP neurons affects their responsiveness to PB chips or how AgRP neurons regulate dopamine release.

Reviewed by eLife

Modulation of pulsatile GnRH dynamics across the ovarian cycle via changes in the network excitability and basal activity of the arcuate kisspeptin network

1. Margaritis Voliotis
2. Xiao Feng Li
3. Ross Alexander De Burgh
4. Geffen Lass
5. Deyana Ivanova
6. Caitlin McIntyre
7. Kevin O'Byrne
8. Krasimira Tsaneva-Atanasova

• Curated by eLife

  Evaluation Summary:

  This manuscript is of considerable interest to neuroendocrinologists and other neuroscientists because it provides important insights into mechanisms controlling the synchronous activity of a specific subpopulation of hypothalamic neurons. Luteinizing hormone is secreted from the pituitary gland in pulses which vary over the estrous cycle. The pulses arise by patterned secretion of a hypothalamic 'releasing factor', the secretion of which is itself governed by a population of hypothalamic neurons that express the neuropeptide kisspeptin. The paper by Voliotis et al. combines novel experimental evidence from transgenic mice with an elegant mathematical model to analyze how the kisspeptin neurons generate the varying pulsatile patterns.

  (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.)

Reviewed by eLife