Neuroscience

Evaluation Summary:

This study asks how diverse signals are integrated at the cellular level to generate adaptive behaviors. The authors show that prolonged food deprivation (i.e. fasting) of C. elegans broadly alters gene expression in food sensing neurons, thereby altering foraging behavior and chemosensory neuron responses to food. The fasting-induced genes include many chemoreceptors, one of which mediates responses to specific volatile components of food. Finally, they show that food controls the expression of a fasting-induced chemoreceptor via multiple external (i.e. sensory) and internal (potentially metabolic) cues. The paper is of importance to scientists with an interest in adaptive behaviour as well as the cellular and molecular mechanisms underlying integration of stimuli.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript bridges neurophysiology and biomechanics and is of broad interest in improving our understanding of insect flight control. Here, Putney et al. record the activity of the flight muscles of tethered hawkmoths and demonstrate that the direction of the visual stimulus to which the insect responds can be classified using precisely timed information on muscle activity from a subset of the flight muscles. This is an important step in identifying the mapping from visual input to motor output, albeit that the mapping identified here is qualitative (i.e. classification of visual stimulus direction) rather than quantitative (i.e. prediction of output torque or apparent angular velocity of self-motion).

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript by O'Herron et al. describes an all-optical method combining optogenetic stimulation and 2-photon microscopy imaging to simultaneously manipulate and monitor brain microvasculature contractility in three dimensions. The method employs a spatial light modulator to create three-dimensional activation patterns in the brains of cranial window-model transgenic mice expressing the excitatory opsin, ReaChR, in mural cells (smooth muscle cells and pericytes). This provides a powerful new in vivo technique to control blood flow into the brain and to understand its actions on brain function.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This study explores the kinetics of heavy metal staining of tissue using time-lapse imaging with X-ray micro computed tomography (CT). It will be of interest to the wide community of scientists preparing biological samples for electron microscopy (EM), in particular large-volume EM. While at present the relation between CT imaging and EM contrast remains to be quantified, this study has the potential to become a reference for the field in establishing a quantitative tool for assessing and developing staining protocols.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper is of potential interest to readers in the fields of working memory and neural coding. It presents a model of a neural circuit that learns to optimally represent its inputs subject to an information capacity limit and claims that this model can account for a range of empirical phenomena in the visual working memory literature. However, the fit to empirical data is qualitative and in some cases unconvincing, certain aspects of the neural model seem difficult to square with established neurophysiology, and there is insufficient conceptual or quantitative comparison with other models in the WM literature that seek to explain the same data.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

The methods presented in this work are of potential broad interest across different domains of human neuroscience. Reliable methods for pushing the limits of spatial resolution for mesoscopic scale imaging of the living human cortex are of wide interest and utility. The image quality and high-spatial resolution of the data are exceptionally high. The paper in its current form demonstrates the application of the developed methods to a few exemplary cortical regions and sequences.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This paper will be of interest to basic and clinical neurophysiologists who are focused on understanding neural mechanisms that influence recovery following spinal cord injury (SCI). The work compares the afferent regulation of motor output to soleus muscle in controls and individuals with SCI. The results indicate differences between groups such that there is less facilitation in the SCI group during muscle contraction.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This study examined the nature of projections from the prefrontal cortex (PFC) to the nucleus accumbens (NAc) and to the ventral tegmental area (VTA). The authors show that PFC projections to NAc and VTA are largely non-overlapping, originate in different layers of PFC, and express different molecular markers. This study provides high-quality data to the long-standing question.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This manuscript shows that it is possible to detect high-abundance peptide antigens in nerve cells at the electron microscope (EM) level in sections of formaldehyde-fixed monkey brain after the sections have been stored for several years in an antifreeze solution in the freezer. The topic of utilizing formalin fixed tissue for research, especially with the numerous "brain banks" worldwide, is an important topic especially if one wishes to conduct studies in post mortem human tissue. The authors used antibodies to detect the presence of vasopressin gene-related products (i.e., neurophysin II and copeptin) in the hypothalamus and pituitary of the monkey brain. This paper is of interest to anatomists who work on AVP neurons in non-human primate. Due to issues with tissue quality, methodology and interpretation, the experimental approach described in this paper may not be as useful for studying fixed and archived brain sections as the authors conclude.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript will be interesting for people performing all optical electrophysiology. It describes a new combination of previously available genetic tools to allow simultaneous optogenetic manipulation and optical electrophysiology. The manuscript does not provide a major conceptual advance but provides good evidence that this assay can be employed for large-scale screening in hIPSC-derived neurons.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript.The reviewers remained anonymous to the authors.)