Neuroscience

eLife assessment

This important study adopts a comprehensive approach: functional connectivity, biochemistry, and psychophysics to reveal a holistic understanding of the relationship between GABA-ergic inhibition in the human MT+ region and visuo-spatial intelligence. The evidence supporting the conclusion is convincing. The result advances our understanding of how the human MT+ is assemble into complex cognition as an intellectual hub, and will be of interest to researchers in psychology, cognitive science, and neuroscience.

eLife assessment

Picard et al. propose a Facial Expression Pain Signature (FEPS) derived from functional magnetic resonance imaging (fMRI) data to predict facial expressions associated with painful heat stimulation. This important work advances our understanding of the brain mechanisms associated with facial expressions of pain. It provides solid evidence that facial expressions of pain contain information that is complementary to other pain-related brain processes. The work will be of broad interest to researchers from varied fields ranging from neurosciences to psychology and affective sciences.

eLife assessment

This is an important study on changes in newborns' neural abilities to distinguish auditory signals at 37 weeks of gestation. The evidence of change in neural discrimination as a function of gestational age is convincing, but, as the authors acknowledge, further control of the acoustic signals and infants' language environment is necessary for the results to be used in clinical applications. The work contributes to the field of neurodevelopment.

eLife assessment

Shore et al. report the important effects of a heterozygous mutation in the KCNT1 potassium channel on ion currents and firing behavior of excitatory and inhibitory neurons in the cortex of KCNT1-Y777H mice. The authors provide solid evidence of physiological differences between this heterozygous mutation and their previous work with homozygotes. The reviewers appreciated the inclusion of recordings in ex vivo slices and dissociated cortical neurons, as well as the additional evidence showing an increase in persistent sodium currents in parvalbumin-positive interneurons in heterozygotes.

eLife assessment

The ThermoMaze represents a valuable tool to control the rest/exploration states of an animal. The data, collected and analyzed using solid and validated methodology, demonstrate its use in addressing previously elusive questions. This will facilitate future work with more in-depth analysis of place cell activity to further support for some of the claims.

eLife assessment

This important study explores how cells maintain subcellular structures in the face of constant protein turnover, focusing on neurons, whose synapses must be kept stable over long periods of time for memory storage. Using proteins from knock-in mice expressing tagged variants of the synaptic scaffold protein PSD95, nanobodies, and multiple imaging methods, there is compelling evidence that PSD95 proteins form complexes at synapses in which single protein copies are sequentially replaced over time. This happens at different rates in different synapse types and is slowest in areas where PSD95 lifetime is the longest and long-term memories are stored. While of general relevance to cell biology, these findings are of particular interest to neuroscientists because they support the hypothesis put forward by Francis Crick that stable synapses, and hence stable long-term memories, can be maintained in the face of short protein lifetimes by sequential replacement of individual subunits in synaptic protein complexes.

eLife assessment

Based on analyses of retinae from genetically modified mice, and from wild-type ground squirrel and macaque, employing microscopic imaging, electrophysiology, and pharmacological manipulations, this valuable study on the role of Cav1.4 calcium channels in cone photoreceptor cells (i) shows that the expression of a Cav1.4 variant lacking calcium conductivity supports the development of cone synapses beyond what is observed in the complete absence of Cav1.4, and (ii) indicates that the cone pathway can partially operate even without calcium flux through Cav1.4 channels, thus preserving behavioral responses under bright light. The evidence for the function of Cav1.4 protein in synapse development is convincing and in agreement with a closely related earlier study by the same authors on rod photoreceptors. The mechanism of compensation of Cav1.4 loss by Cav3 remains unclear but appears to involve post-transcriptional processes. As congenital Cav1.4 dysfunction can cause stationary night blindness, this work relates to a wide range of neuroscience topics, from synapse biology to neuro-ophthalmology.

eLife assessment

This is a conceptually appealing study in which the authors identify genes whose function is important for the development of inhibitory (GABA) neurons, and then demonstrate that a diet rich in ketone body β-hydroxybutyrate partially suppresses specific mutant phenotypes. The authors provide compelling evidence that features methods, data and analyses more rigorous than the current state-of-the-art. Conceptually, this is evidence of a rescue of a developmental defect with dietary metabolic intervention, linking, in an elegant way, the underpinning genetic mechanisms with novel metabolic pathways that could be used to circumvent the defects.

eLife assessment

This important work shows compelling data that significantly advances our understanding of the regulation of neurotransmitter and hormone secretion by exploring the mechanisms of how the protein complexin 2 (Cplx2) interacts with the calcium sensor synaptotagmin. The function of mammalian Cplx2 is studied using chromaffin cells derived from Cplx2 knock out mice as a system to overexpress and functionally characterize mutant Cplx2 forms and the interaction between Cplx2 and synaptotagmin. The authors identify structural requirements within the protein for Cplx's dual role in preventing premature vesicle exocytosis and enhancing evoked exocytosis. The findings are of broad interest to neuroscientists and cell biologists.

eLife assessment

The paper investigates a potential cause of a type of severe epilepsy that develops in early life because of a defect in a gene called KCNQ2. The significance is fundamental because it substantially advances our understanding of a major research question. The strength of the evidence is convincing because appropriate methods are used that are in line with the state-of-the art.