Neuroscience

eLife assessment

Cover et al., examine the pathway from the intralaminar nucleus of the thalamus (rILN) to the dorsal striatum (DS) in the reinforcement of behavior/actions. The rILN sends a large glutamatergic projection to the DS, but its role in action selection was unknown. The authors found that the rILN neurons that project to the DS were activated at both action initiation and with the reward. Activation and inhibition of this pathway increased the success or decreased the success of reward acquisition, respectively. The findings are an important advance our understanding of the function of rILN to DS projection in reward-based behavior. The manuscript has provided convincing evidence with the appropriate methodologies to support these claims.

eLife assessment

This study presents a valuable finding in identifying the roles of the pericytes in maintaining vascular volume and integrity of spiral ganglion neurons (SGNs) in the cochlea, the main hearing organ. The evidence supporting the authors' claims is solid using an inducible and conditional pericyte depletion mouse model and the co-culture models. While the study provides a modest translational contribution, understanding the roles of organ-specific pericytes is paramount, making this study timely and significant. The work will be interesting for biomedical biologists working on hearing, blood vessels, signaling, and cell-to-cell interactions.

eLife assessment

This paper will be of interest to developmental biologists who study the gene regulatory mechanisms necessary for neuronal identity and circuit assembly. The study presents important findings regarding the role of the LIM homeodomain transcription factor Isl2 in the development of spinal motor neurons. While the importance of Isl2 for the acquisition of axial and visceral motor neuron development was already described in the literature, the data convincingly describe an additional role in the differentiation of a subset of limb-innervating motor neurons.

eLife assessment

This study reports an important new resource, MHC class I and MHC class II reporter mice, which provide a means to monitor MHC activation in vivo. The authors use these mice to study inflammatory demyelination in two mouse models of multiple sclerosis. The study provides a compelling demonstration of the new reporter lines as a valuable tool for analysis of inflammation and neurodegeneration.

eLife assessment

This manuscript presents a valuable new approach to modelling patterns of brain activity evoked by non-invasive brain stimulation, shedding light on how such stimulation drives neuronal dynamics. The performance of the model is impressive and its validity is supported by solid evidence. This work will be of interest to researchers working in computational neuroscience, neuroimaging, and non-invasive brain stimulation.

eLife assessment

This manuscript will be of interest to both developmental biologists and neuroscientists. The data suggest that most (but not all) neuronal types are present in both Drosophila sexes, and the existence of mostly shared scSeq clusters suggests that sex-specific versions of the transcription factor Fruitless can modify neural function in a sex-specific way without completely altering core neural identity. This cell type gene expression atlas should prove valuable in future efforts to understand mechanisms of sex-specific development, as well as the molecular and developmental-genetic basis of sex differences in behaviour.

eLife assessment

Detailed electron-microscopy reconstructions of neurons, which are now available for a complete Drosophila central brain, raise the prospect of detailed models of their electrical properties. This manuscript uses a recently released dataset to model one particular neuron in an olfactory learning center of the fly brain. The model elucidates how this neuron responds to synaptic inputs that represent odor, suggesting how modification of these synapses might underlie olfactory memory. This work brings together electrophysiological recordings and neuroanatomical reconstructions from volume electron microscopy to model how a neuronal arbor integrates synaptic inputs. With the many ongoing connectome mapping projects world wide, the results here can illustrate an approach to interpretation of connectomes towards understanding neural circuit function. The rules of synaptic plasticity discussed here furthermore do not only shed light into the mechanisms of learning and memory in biological systems but also inspire the formulation of new approaches to adjusting connection weights in artificial neural networks.

eLife assessment

In this study, Diehl and Redish present a novel account of functional variability in the rodent medial prefrontal cortex. The authors report that, in general, the dorsal regions encode decision-related variables, whereas the ventral regions encode variables more linked to motivation, such as trial number in the session and amount of lingering time. Overall, the study is interesting, the experimental design is excellent, and the uniquely large neural data set is a strength. The suggestion of functional subdivisions in the prelimbic area is particularly provocative, and this conclusion, along with the data supporting it, will be of broad interest to those who study the anatomy and function of the rodent medial prefrontal cortex.

eLife assessment

This manuscript provides a solid and valuable analysis of the advantages and potential pitfalls of the application of Granger Causality to calcium imaging data that should be of interest to a wide range of neuroscience researchers. Granger Causality is a key tool in assessing the temporal relationships between variables, but one that is susceptible to many types of artifacts. The rigor of the authors' application of the methodology to calcium imaging data in particular leads to a more robust understanding of the effects of measurement artifacts and analysis choices on the results. There was some concern, however, about whether all of the findings would apply outside feedforward neural circuits and it was unclear how some of the results relate to others that currently exist in the literature.

eLife assessment

This article presents a model that uses spike timing-dependent plasticity and theta phase precession of spiking neurons to generate representations similar to those learned by temporal difference learning to form successor representations. This work is important for bridging between biologically detailed mechanisms shown in experimental data and the more abstract models in the reinforcement framework literature. The simulations are compelling, but several aspects may rely on unrealistic assumptions, so further work is necessary to determine whether such a learning process could actually occur in the brain.