Neuroscience

Evaluation Summary:

Second order conditioning is a higher form of learning where a previously conditioned stimulus (e.g. odor A by food) is used to condition the perception of another stimulus (e.g. odor B by odor A). Yamada et al. have used the fly to identify a neural circuit in the insect mushroom body underpinning second order conditioning. This work elegantly combines neural circuit mapping, electrophysiology and modeling to put forward a mechanistic model for this highly conserved form of learning.

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:

The authors measured the heartbeat and touch perception while people touched a variety of surfaces. The results indicate that people's heart rates and heartbeats vary systematically according to the type of touch performed and how difficult it was to perceive the grooved surfaces. The paradigm and the results appear very interesting though the specific analyses of choice and their presentation require some improvement to make a more convincing case.

(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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript contributes to a circuit-based understanding of how sweet and bitter tastes are integrated with hunger state to drive feeding initiation in Drosophila. Anatomical, behavioral, and neuronal activity data support a multi-step pathway from sensory input to motor output. This manuscript, thus, contributes to our understanding of how multiple sensory cues are integrated with an internal state to reach a behavioral decision.

(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:

In this paper, Ekman and colleagues present novel evidence, using a visual sequence task in fMRI, that the early visual cortex (V1) and the hippocampus both represent perceptual sequences in the form of a predictive "successor" representation, where the current state is represented in terms of its future (successor) states in a temporally discounted fashion. In both brain structures, there was evidence for upcoming, but not preceding steps in the sequence, and these results were found only in the temporal but not spatial domain. This study suggests that the hippocampus and V1 represent temporally structured information in a predictive, future-oriented manner.

(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:

Haggerty et al. reported findings examining how changes in brain function are involved in alcohol binge drinking, with a selective focus on the synaptic and circuit alterations that occur in the anterior insular cortex inputs within the dorsolateral striatum. They show that chronic alcohol drinking produces glutamatergic synaptic adaptations and by stimulating this circuit, binge drinking could be reduced without altering either water consumption or general performance for select reinforcing, anxiogenic or locomotor behaviors. The results of this study may specifically improve our understanding of the neurocircuitry mediating a common alcohol use disorder associated behavior referred to as "front-loading" or excessive drinking during the very beginning of the session.

(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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper is of interest to a broad range of neuroscientists, particularly those interested in ApoE biology and Alzheimer's disease (AD), as it reveals a novel mechanism that counteracts AD-linked amyloid plaque burden and synapse dysfunction in mice. Overall, the methodology is sound, sophisticated, and employs animal models that more closely mimic human diseases, and the results are interesting and compelling. Whilst the mechanistic hypothesis proposed by the authors is consistent with the data, plausible alternative explanations remain.

(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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript presents a method to characterize diverse neural activity patterns arising from a small invertebrate circuit. This is of practical interest to invertebrate neuroscientists. The application of unsupervised methods to characterize qualitatively distinct regimes of spiking neural circuits is very interesting. The challenges and lessons learned in this study are therefore of broader interest to those seeking to quantitatively characterize large sets of neural data across many subjects. The survey could be improved by further validation of the derived clusters.

(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:

There has been a great deal of recent interest in the neural basis for offset responses given their hypothesised importance to perception. This tests the relevance of offset responses to duration perception in a mouse model in addition to examining the brain basis. The work is thorough and well executed. The work demonstrates offset responses that occurs for the first time in auditory cortex distinct from A1 where prevention of offsets by activating cells causes worsening of behavioural performance.

(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 manuscript shows an important role for Cav2.3 channels in SNI-mediated allodynia and firing properties of PV-expressing APT neurons. Mechanisms that underlie adaptations in chronic pain models are extremely important for the development of novel therapeutics for chronic pain and this could be a significant contribution in that regard. However, the discussion asserts that these studies are the "first direct evidence that supra-spinal Cav3.2 channels play a fundamental role in pain pathophysiology." This is an overstatement as Chen and colleagues examined the role of these channels in the anterior cingulate cortex in CCI-mediated neuropathic pain (Shen, et al., 2015, Molecular Pain).

(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 investigates the neural basis of the hidden causal structure between visual and proprioceptive signals in the primate premotor and parietal circuit during reaching tasks executed in a virtual reality environment, where information between the two modalities can be dissociated. Modelling is used to characterize the proprioceptive drift of the monkeys when integrating bimodal information. The key novel result is that premotor neurons represent the integration of bimodal information for small disparities and the segregation for large disparities between the proprioceptive and visual information, while parietal cells show reaching tuning changes that support the updating sensory uncertainty between tasks. Overall, the experiments are technically sound, and the conclusions are mostly well supported. However, a simpler framing of the paper could make the main message easier to grasp, the analysis of Bayesian models seems to lack major details, the statistical reporting is below standard, and a large part of the extensive literature on the role of premotor and parietal cortex in visuomotor behavior is lacking.

(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.)