Neuroscience

Evaluation Summary:

This pre-registration study by Kerrén et al. used a proactive interference task in combination with MEG recordings on humans to test predictions of a previous computational model postulating that neural representations of competing memories are associated with varied phases of the hippocampus theta-band rhythm. Their results largely confirmed the hypothesis and suggest that reactivations of target and competitor memories indeed occur at different phases of theta oscillations, which is further related to the intrusion effect in behavior.

(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.)

Evaluation Summary:

Using an elegant combination of cutting-edge techniques, the authors show that in the neuromuscular junction of the nematode C. elegans two different classes of voltage-activated calcium channels differentially trigger exocytosis of distinct pools of synaptic vesicles, one docked to the active zone and a second one localized more distant from the active zone. These findings will be of broad interest to neuroscientists interested in the mechanisms of calcium-mediated release of neurotransmitters at chemical 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 #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

eLife assessment

This is an important study on the role of the Ras/MEK/Erk signaling cascade in brain development, with both theoretical and practical implications in multiple fields. The authors reveal functional redundancy and shared function for Erk1 and Erk2 in determining medial ganglionic eminence derived glial number, and exclude a role for Erk1 and Erk2 in the regulation of GABAergic neuron number or initial specification of GABAergic identity. They combine multiple methods including Ribotags, electrophysiology, and chemogenetic stimulation using DREADDs towards comprehensive conclusions. Reviewers expressed concerns about the coherence of the findings, and about the selection of controls mouse lines. Heterozygous ERK1/2 mice are used as 'het controls' throughout the manuscript, however, reviewers felt that there was not sufficient evidence that ERK levels in heterozygous mice are similar to wildtype mice. Nevertheless, these compelling findings will be of interest to a broad readership, and especially readers interested in kinase function and neurodevelopmental syndromes.

eLife assessment

This important study reports selective CDKL5 inhibitors that may be of high interest to investigate the role of this kinase in disease (particularly, in CDKL5 deficiency disorder) and to address unsolved issues of inconsistency in the phenotypic characterization of CDKL5-deficient knockout mice. The evidence supporting the conclusions is convincing, with rigorous biochemical, in vitro and ex vivo assays. The work will be of interest to cell and medical biologists and epileptologists working in the fields of epilepsy and neural excitation.

eLife assessment

This is important work analyzing the trial-by-trial progression of learning, and how the outcome of one trial influences cortex-wide neural responses on the next trial. However, the evidence for the central claims is incomplete because the potential confounds of slow hemodynamic effects and behavioral changes induced by the previous trial were not adequately addressed.

eLife assessment

This is an important study of the dimensionality and synchrony of calcium responses in Purkinje cells measured across a large region of the cerebellar cortex over the course of learning. This work has the potential to inform our understanding of the functional organization of the cerebellum and longstanding hypotheses about the role of cerebellar climbing fibers in the induction of learning and in the timing of movement, but the evidence provided for the many sweeping claims is incomplete. The paper would benefit from additional statistical analyses to more rigorously evaluate the central claims, with consideration of appropriate comparison groups and potential confounds.

Evaluation Summary:

Keine et al study the role of the RhoGTPase Rac1 in neurotransmitter release by ablating this protein at an age when synapses are in an almost mature stage. They describe an increase in synaptic strength, which they interpret as an increase in release probability or fusogenicity of synaptic vesicles. They also describe subtle effects in the timing of release, which point towards a mild defect in positional priming. The study delivers important information on the role of Rac1.

(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.)

Evaluation Summary:

The current study examined in detail the role of oxytocin neurons in the hypothalamus in regulating food intake. The current study extends our understanding of the role of this peptide in regulating complex behaviors.

(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.)

Evaluation Summary:

Recent studies of the brainstem locus coeruleus (LC) noradrenaline system have demonstrated a partially modular organization in which specific classes of neurons can serve distinct functions or exhibit module-specific co-activity. However, how noradrenaline cell classes function in a modular way is not clear. The authors have accomplished a technical feat by recording up to eight LC neurons at once using ex-vivo, multi-patch recordings. In doing so, two empirically-derived classes of LC neurons were identified and the analysis of electrical coupling between these neurons established some principles of local circuit communication occurring preferentially within the defined cell classes.

(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.)