Neuroscience

eLife assessment

This manuscript examines shared and divergent mechanisms of disruptions of five different mTOR pathway genes on embryonic mouse brain neuronal development. The significance of the manuscript is important, because it bridges several different genetic causes of focal malformations of cortical development. The strength of evidence is compelling, relying on both gain and loss of function, demonstrating differential impact on excitatory synaptic activity, conferring gene-specific mechanisms of hyperexcitability. The results have both theoretical and practical implications for the field of developmental neurobiology and clinical epilepsy.

eLife assessment

This important paper sheds light on the role of expectations in perceptual decision-making. Sophisticated analyses of human EEG data provide convincing evidence that both motor preparation and sensory processing were affected by expectations, albeit with different time courses. These findings will be of interest to scientists interested in perception and decision-making.

eLife assessment

This study provides a valuable contribution to understanding the neural mechanisms underlying age-related changes in attention and speech understanding. The large dataset (N=105) provides convincing evidence for how speech recognition behaviour and neural tracking of speech separately evolve in about 2 years. The work would be of interest to psychologists, neuroscientists, and audiologists.

eLife assessment

The authors used an innovative modified 10X genomic sequencing method to detect cPCDHg is-forms in pyramidal neurons. With solid electrophysiological recordings, they showed that neurons expressing the same sets of cPCDHg isoforms are less likely to form synapses with each other. These valuable findings confirms previous results and extend our understanding of cPCDHg diversity and neuronal connectivity.

eLife assessment

This important paper provides solid evidence that the angular gyrus plays a role in insight-based memory updating. The study is well conducted, timely, and presents clear-cut behavioral results. While the study provides robust evidence that transcranial magnetic stimulation to the angular gyrus impacts memory, evidence for the strong claim of a causal contribution of the angular gyrus in particular – apart from other connected regions, including the hippocampus – is not conclusive.

eLife assessment

This important multicenter study provides convincing evidence that the auditory noise emitted during online transcranial ultrasound stimulation (TUS) protocols can pose a considerable confound and is able to explain corticospinal excitability changes as measured with Motor Evoked Potentials (MEP). The findings lay the ground for future studies optimising protocols and control conditions to leverage TUS as a meaningful experimental and clinical tool. A clear strength of the study is the multitude of control conditions (i.e., control sites, acoustic masking, acoustic stimulation). These findings will be of interest to neuroscience researchers using brain stimulation approaches.

eLife assessment

This study characterized the activity of optogenetically identified dopaminergic and GABAergic neurons in the ventral tegmental area in mice performing a memory-guided T-maze task, and shows that subpopulations of dopaminergic and GABAergic neurons exhibited choice-related activity during the delay period, consistent with some previous studies (e.g. Morris et al., 2006, Parker et al., 2016). The authors demonstrate that these delay-period activities were enhanced when the task requires short-term memory. The results are convincing and this study provides important results regarding the nature of delay-period activity in the task.

eLife assessment

This manuscript addresses a non-canonical function of the Class 2 ribonuclease III Drosha in the regulation of adult neural stem cell fate, important for understanding how these cells generate neurons or oligodendrocytic cells.
Overall, this manuscript has many strengths. The authors identify 165 proteins, several of them enriched in neural stem cells, and potentially specific for miRNA dependent or independent Drosha macromolecular complexes.
While the authors provide systematic and convincing evidence on the biochemical interactions among the key players in this cascade, the significance of these interactions for neural stem cell fate determination in vivo remains unclear, as the in vitro cellular systems used to document most of the data reported in the paper may not (fully) represent resident neural stem cells in the adult hippocampus. The in vivo function mediated by Drosha/ Safb1 needs to be substantiated by more evidence and/or complementary approaches.

eLife assessment

In this important study, the authors explore the importance of developmental changes in cortico-DRN innervation in the balance of behavioral control in a foraging task. The authors report somewhat convincing evidence that while juvenile mice and adult mice both perform the task, juveniles exhibit more impulsive behavior due to reduced efficacy of cortico-DRN projections. The authors conclude that the development of cortico-DRN (esp mPFC) projections allows 5HT input to promote perseveration (or exploitation) in the balance of behavioral control. However, reviewers raised issues regarding the strength of the evidence without further experiments.

eLife assessment

This study addresses the long-standing question as to how different functional pools of synaptic vesicles are organized in presynaptic terminals to mediate different modes of neurotransmitter release. Based on imaging of active synapses with recycling synaptic vesicles labeled by FM-styryl dyes, the authors provide data that are compatible with the hypothesis that two separate reserve pools of vesicles – slowly vs. rapidly mobilizing – feed two distinct releasable pools – reluctantly vs. rapidly releasing. Overall, this study represents a valuable contribution to the field of synapse biology, specifically to presynaptic dynamics and plasticity. The authors' methodological approach of using bulk FM-styryl dye destaining as a readout of precise vesicle arrangements and pools in a population of functionally very diverse synapses has limitations. Consequently, the evidence that directly supports the authors' two-pool-interpretation of their data is incomplete, and alternative interpretations of the data remain possible.