Neuroscience

eLife Assessment

This important collection of over 800 new cell type-specific driver lines will be an invaluable resource for researchers studying associative learning in Drosophila. Thoroughly characterized and well documented, this collection will permit researchers to selectively target neurons that deliver information to, or receive it from, the memory center of the fly brain called the Mushroom Body. Given the wealth of new drivers and the genetic access they provide to over 300 cell types, this compelling work will be of interest not only to researchers studying the mechanisms of associative learning but more generally to those dissecting sensorimotor circuits in the fly nervous system.

eLife Assessment

This study provides important insights into the brain activity and connectivity underlying speech comprehension, revealing three brain states. The authors present compelling evidence by leveraging hidden Markov modeling of fMRI data to link brain state dynamics to comprehension scores, though the functional role of these states remains under-explored. These findings advance our understanding of how brain state transitions in narrative comprehension relate to stimulus-specific features.

eLife Assessment

This paper presents useful results that extend our understanding of how the visual cortex encodes temporal structure, providing new information about sequence representations in the upper layers of the visual cortex. The evidence for prediction errors is solid, however, support for other claims regarding sparsification and simplification of activity following training is incomplete. The main concerns pertain to the confounds associated with restricted ordering within blocks that does not allow for separate plasticity mechanisms operating on different time scales.

eLife Assessment

This paper addresses an important topic (normative trajectory modelling), seeking to provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on a pre-trained population normative model. The evidence provided for the new methods is solid.

eLife Assessment

Yonk and colleagues provide a valuable, timely, and in-depth study showcasing the role of thalamostriatal inputs in learning and action selection. After characterizing the synaptic properties of these inputs onto different striatal cell types in vitro, they provide solid evidence that posterior medial thalamic nucleus (POm) terminals in striatum are activated during reward expectation and arousal. The overall function of this pathway and the degree to which results are confounded by viral contamination of surrounding nuclei and movements remain open questions.

eLife Assessment

Somatostatin-expressing neurons of the entopeduncular nucleus (EPNSst+) provide a limbic output of the basal ganglia and co-release GABA and Glutamate in their projection to the lateral habenula, a structure that is key for reward-based learning. Combining fiber photometry and computational modeling, the authors provide compelling evidence that EPNSst+ neural activity represents movement, choice direction and reward outcomes in a probabilistic switching task but, surprisingly, neither chronic genetic silencing of these neurons nor selectively elimination glutamate release affected behavioral performance in well-trained animals. This valuable study shows that despite its representation of key task variables, EPNSst+ neurons are dispensable for ongoing performance in a task requiring outcome monitoring to optimize reward. This work will be of interest to those interested in neural circuits, learning, and/or decision making.

eLife Assessment

Cav2 voltage-gated calcium channels play key roles in regulating synaptic strength and plasticity. In contrast to mammals, invertebrates like Drosophila encode a single Cav2 channel, raising questions on how diversity in Cav2 is achieved from a single gene. Here, the authors present solid evidence that two alternatively spliced Cac isoforms enable important changes in Cav2 expression, localization, and function in synaptic transmission and plasticity at the Drosophila neuromuscular junction. How the isoforms affect synaptic calcium channel levels remains less clear. This study provides insights into the roles of voltage-gated calcium channel splice isoforms in synaptic transmission.

eLife Assessment

This valuable study uses a novel method to record spine calcium responses without the confounds of backpropagating action potentials to study how the dendritic integration of large numbers of inputs generates the tuned output of cortical neurons. While the results are generally solid, the study would benefit from more details, characterizations, and quantifications, including better validation of the method to suppress backpropagating action potentials.

eLife Assessment

This valuable study by Cui et al. investigates mechanisms generating sighs, which are crucial for respiratory function and linked to emotional states. Utilizing advanced methods in mice, they provide solid evidence that increased excitability in specific preBötzinger complex neuronal subpopulations expressing Neuromedin B receptors, gastrin-releasing peptide receptors, or somatostatin can induce sigh-like large amplitude inspirations. With additional technical clarifications and further elaboration of the limitations in terms of how the results are interpreted in the revised manuscript, the study will interest neuroscientists studying respiratory neurobiology and rhythmic motor systems.

eLife Assessment

In this revised manuscript, Dong et al. investigate the role of the small Ras-like GTPase Rab10 in the exocytosis of DCVs in mouse hippocampal neurons, showing that Rab10 depletion hinders DCV exocytosis independently of its effects on neurite outgrowth. Upon revising their work, these findings provide compelling evidence that Rab10 depletion leads to altered ER morphology, impaired ER-based calcium buffering, and decreased ribosomal protein expression, which collectively contributes to defective DCV secretion. The study comes to the fundamental conclusion that Rab10 is critical for DCV release by ensuring ER calcium homeostasis.