Neuroscience

Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock

1. Andrea Brenna
2. Micaela Borsa
3. Gabriella Saro
4. Jürgen A Ripperger
5. Dominique A Glauser
6. Zhihong Yang
7. Antoine Adamantidis
8. Urs Albrecht

• Curated by eLife

  eLife Assessment

  This important chronobiological study in mice suggests that light modulated activity of Cdk5 activity on the PKA-CaMK-CREB signaling pathway provides missing molecular mechanistic details to understand light-induced circadian clock phase delays during the early night, but not for phase advances in the morning. The authors provide convincing evidence bridging from behavioral to molecular/cellular experiments to neural activity imaging.

Reviewed by eLife

Change point estimation by the mouse medial frontal cortex during probabilistic reward learning

1. Cayla E Murphy
2. Hongli Wang
3. Heather K Ortega
4. Alex C Kwan
5. Huriye Atilgan

• Curated by eLife

  eLife Assessment

  This study examined the role of the dorsal medial prefrontal cortex of mice in anticipating reward-value switch points in a two-armed bandit task. They demonstrate the dorsal medial prefrontal cortex is involved in task performance and use model-based methods to uncover the algorithmic processes affected by prefrontal cortex perturbations. If the claims were supported, this would be a valuable finding. Unfortunately, the reviewers recognised significant issues with the task design and analyses, making the evidence to support the role of the prefrontal cortex in anticipation of switches inadequate.

Reviewed by eLife

Glucocorticoids desensitize hypothalamic CRH neurons to norepinephrine and somatic stress activation via rapid nitrosylation-dependent regulation of α1 adrenoreceptor trafficking

1. Grant L Weiss
2. Laura M Harrison
3. Zhiying Jiang
4. Alyssa M Nielsen
5. Maximillian S Feygin
6. Sandy Nguyen
7. Parker S Tirrell
8. Jeffrey Tasker

• Curated by eLife

  eLife Assessment

  This manuscript describes work that is fundamental to our understanding of the mechanism of how stress regulates the noradrenergic system and the CRH system. Using a combination of ex vivo physiology and in vitro methods, the study provides compelling evidence as to the signaling mechanisms of how glucocorticoids impact adrenergic GPCRs in CRH cells via receptor trafficking. While the ex vivo work is specific to the hypothalamus, the mechanisms here could be extrapolated and investigated in other brain regions that may have similar signaling regulation.

Reviewed by eLife

Cold induces brain region-selective cell activity-dependent lipid metabolism

1. Hyeonyoung Min
2. Yale Y Yang
3. Yunlei Yang

• Curated by eLife

  eLife Assessment

  This phenomenological study reported that cold exposure induced mRNA expression of genes related to lipid metabolism in the paraventricular nucleus of the hypothalamus (PVH). While the paper does not address cell-type specificity or the functional role of lipids in PVH, the findings might still serve as a useful basis for others to explore their relevance to brain responses to cold. In the revised manuscript, the authors made adequate editions, such as new immunostaining and immunoblotting of AGTL and HSL in the PVH, and pharmacological inhibition of lipid peroxidation and lipolysis. The authors also increased the sample size of some experiments and revised the text to limit their data interpretation. Thus, the reviewers considered that these studies are solid in conclusively describing how the PVH is reprogrammed at the level of gene expression by cold exposure.

Reviewed by eLife

High-Resolution Laminar Identification in Macaque Primary Visual Cortex Using Neuropixels Probes

1. Li A Zhang
2. Peichao Li
3. Edward M Callaway

• Curated by eLife

  eLife Assessment

  This important study provides insights and strategies for assessing laminar structure in vivo in the visual cortex of the macaque monkey with high-density linear electrode arrays. The paper provides convincing evidence demonstrating that signals in higher frequency bands, related to the discharge of action potentials, are of substantially better use for achieving well-resolved cortical layer identification than are signals in lower frequency bands typically associated with local field potentials and standard-practice Current Source Density (CSD) analyses. These findings are of interest to a wide range of neuroscientists making comparisons between cortical layers or recording with array electrodes.

Reviewed by eLife

Commissureless acts as a substrate adapter in a conserved Nedd4 E3 ubiquitin ligase pathway to promote axon growth across the midline

1. Kelly G Sullivan
2. Greg J Bashaw

• Curated by eLife

  eLife Assessment

  This work is of fundamental significance to the field of nervous system development as it advances our mechanistic understanding of axon guidance. The rigorous biochemical and genetic approaches are compelling, experiments are well-controlled, and the major claims are supported by convincing data. The study should be of general interest to the developmental neurobiology community.

Reviewed by eLife

In vitro survival and neurogenic potential of central canal-derived neural stem cells depend on spinal cord injury type

1. Lars Erik Schiro
2. Ulrich Stefan Bauer
3. Christiana Bjorkli
4. Axel Sandvig
5. Ioanna Sandvig

Reviewed by PREreview

Dynamic reinforcement learning reveals time-dependent shifts in strategy during reward learning

1. Sarah Jo C Venditto
2. Kevin J Miller
3. Carlos D Brody
4. Nathaniel D Daw

• Curated by eLife

  eLife Assessment

  This important work by Veneditto and colleagues developed a new modeling approach, called a mixture-of-agent hidden Markov model (MoA-HMM), in which choice behaviors are modeled as transitions between discrete states defined by different weighting of several reinforcement learning and decision strategies. The authors apply this approach to their previous data collected from rats performing the two-step task, and show that this method predicts fluctuations in neural and other behavioral data and provides better fits to the data than previous methods. The revision has greatly improved the manuscript, the evidence supporting the conclusions is convincing, and the method is of general interest to the field.

Reviewed by eLife

A memory model of rodent spatial navigation in which place cells are memories arranged in a grid and grid cells are non-spatial

1. David E Huber

• Curated by eLife

  eLife Assessment

  This important paper provides solid evidence for an alternative conceptualization of the functional role of the place and grid cell network in the medial temporal lobe for memory as opposed to spatial processing or navigation. The theory is extensive, tightly integrating data on various spatial cell types. It accounts for many experimental results and generates strong predictions for future studies that will be of interest to researchers in this field. The impact of the work would be strengthened if future experiments reveal that grid cells do indeed encode specific nonspatial features.

Reviewed by eLife

The interplay between homeostatic synaptic scaling and homeostatic structural plasticity maintains the robust firing rate of neural networks

1. Han Lu
2. Sandra Diaz-Pier
3. Maximilian Lenz
4. Andreas Vlachos

• Curated by eLife

  eLife Assessment

  This valuable study combines experiments and modelling to advance our understanding of the nonlinear nature of homeostatic structural plasticity and its interaction with synaptic scaling. The methodology and findings are solid, although additional work is needed to better link models with experiments and support some of the conclusions drawn. This study will be of interest to theoretical and experimental neuroscientists working in homeostatic plasticity.

Reviewed by eLife