Neuroscience

eLife Assessment

This is an important study demonstrating that anosmia in Parkinson's disease patients is due to dysfunction in cholinergic neurons. This study provides compelling evidence, using scRNA sequencing, that cholinergic olfactory projection neurons (OPN) are consistently affected in five different fruit fly models of Parkinson's disease, exhibiting synaptic dysfunction before the onset of motor deficits. Comparisons with scRNA sequencing of patients' human brain samples reveals similar synaptic gene deregulation in cholinergic neurons of patients. This study points the possibility that targeting cholinergic neurons could be a potential avenue for early diagnosis and intervention in PD.

eLife Assessment

This important study is an advancement towards the understanding of animal nervous system organization and evolution by providing an exceptional, high-quality and detailed description of the entire connectome of the 3-day larva of the marine annelid Platynereis dumerilii. It provides a wealth of data on cell type diversity and the modules that interconnect them. Its strength is the massive amount of high-quality data, although this is also partly a weakness as it can make the work difficult to read and digest scientifically. This work lays the foundations for studies on cell type diversity, segmental vs. intersegmental connectivity, and mushroom bodies, but will certainly also be of use to scientists interested in other nervous systems parts, their functions, and evolution.

eLife Assessment

This study provides important findings on the nature of eye movement choices by human subjects. The study uses a novel approach and provides relatively clear and convincing results of the relationship between pupil size and saccade production. The results should be of interest to a broad audience interested in sensorimotor integration and sensory-guided decision-making.

eLife Assessment

This manuscript presents valuable findings showing that rapamycin directly activates the cool-sensing ion channel, TRPM8, acting through a different binding site than other small-molecule cooling agents such as menthol. The use of Ca2+-imaging, electrophysiology, and computational biology provides solid evidence to support the finding. The authors also present a novel NMR-based method to help identify details of the binding site interactions. In this revised version, some analysis and the presentation have been corrected and improved. Their findings provide insights into TRP channel pharmacology and may indicate previously unknown physiological effects or therapeutic mechanisms of the immunosuppressant, rapamycin.

eLife Assessment

This useful study aimed to examine the relationship of spatial frequency selectivity of single macaque inferotemporal (IT) neurons to category selectivity. Interesting findings in this report suggest a shift in preferred spatial frequency during the response, from low to high spatial frequencies. This agrees with a coarse-to-fine processing strategy, which is in line with multiple studies in the early visual cortex. Some of the findings were difficult to evaluate because the methods are incomplete. The conclusion that single-unit spatial frequency selectivity can predict object coding requires further evidence to confirm.

eLife Assessment

This important study identifies species- and sex-specific neuronal cell types and gene expression in the preoptic area (POA) to help understand the evolutionary divergence of social behaviors. The evidence from single-nucleus RNA sequencing and immunostaining is compelling and suggests that cellular differences in the POA may contribute to behavioral variations such as mating and parental care that are apparent in two closely related deer mouse species. These rich observations provide an entry point for future hypothesis-driven experiments to demonstrate a causal role for these populations in sex- or species-variable behaviors in vertebrates. These data will be a resource that is of value to behavioral neuroscientists.

eLife Assessment

This is a valuable study, tackling the long-standing issue of the difficulty in imaging the inferior olive and addressing the most relevant questions with a rigorous approach. The technological advance allowed the authors to generate solid experimental evidence with high-quality data. The results are presented clearly and the analyses are rigorous.

eLife Assessment

This study investigates trial-by-trial inter-areal interactions in the visual cortex of the mouse and the monkey by analyzing two previously published datasets. The authors find that activity in one layer (in mice) or one area (in monkeys) can partially predict neural activity in another layer or area on the single-trial level in different experimental contexts. This valuable finding expands previously known contributions of stimulus-independent downstream activity to neural responses in the visual cortex by demonstrating how these change under varying visual stimuli as well as in the absence of visual stimulation. While the methodology is solid, the analysis for the monkey data is incomplete and would benefit from including a second animal.

eLife assessment

The study presents a useful computational analysis of how the ratio between excitatory and inhibitory neural numbers affects coding capacity. The authors show that increasing the proportion of inhibitory neurons (as observed in upper cortical layers compared to the input recipient layer 4) increases the dimensionality of neural activity and improves the encoding of time-varying stimuli. However, the evidence about the role of the inhibitory population in coding is incomplete because numerical results are neither supported by analytical mathematical results nor include controls for changes in firing thresholds or subtypes of inhibitory neurons.

eLife Assessment

This study presents useful findings on the differences between male and hermaphrodite C. elegans connectomes and how they may result in changes in locomotory behavioural outputs. However, the study appears incomplete with respect to the relationship between sex-specific AVA wiring and male mate-finding. Another area of concern is that the analysis does not consider animal-to-animal variability in the wiring when attempting to identify significant differences between the male and hermaphrodite.