Neuroscience

Evaluation Summary:

This manuscript suggests that the neuronal circuit from the basal amygdala (BA) to the ventral hippocampus (VH) consists of both excitatory and inhibitory projections to specific targeted areas. The main message is that excitatory input specifically targets VH neurons that in turn project to the BA and nucleus accumbens (NA). In contrast, BA inhibitory input preferentially targets VH neurons that project to the BA to gate place-value associations. The reviewers agree that the manuscript reports potentially interesting data. However, they all agree that the claim made is preliminary and only partially sustained by the submitted experimental evidence.

(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:

The study of cortical regulation of behavior under conflict is novel, timely, and important. It is of broad interest to neuroscientists studying the neural substrates of fear and reward and offers a novel behavioural perspective showing how these opposing motivational states interact to influence behaviour differentially across individuals and how this is regulated by glutamatergic and GABAergic neurons in the prefrontal cortex. The paper uses a variety of cutting-edge tools to dissect the microcircuits of the prefrontal cortex. The claims are generally supported by the data, but some claims comparing individual differences require additional statistical analyses and consideration of potential alternative interpretations for the behavioral phenotypes observed.

(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:

The authors develop a new technique allowing simultaneous imaging of hippocampal subfields in behaving mice. This paper will be of interest to the large number of neuroscientists who study the hippocampal circuit, and more broadly to those interested in methods to enable high-resolution in vivo imaging across depths in the brain.

(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 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This study is of broad interest to neuroscientists interested in membrane excitability and translational biologists and physicians eager for robust animal models for disorders involving mutations in the KCNMA gene, such as paroxysmal nonkinesigenic dyskinesia PNKD3. Here, phenotypes of mouse models of three of the more common patient disease-related mutations in KCNMA are evaluated for similarities to patient phenotypes. This work establishes that BK channel mutations linked to human neurological disease can, on their own, cause similar pathology in mice, and it also begins to provide neurological bases for the associated behavioral deficits. Importantly, one of the mutant alleles expressed in mice most closely phenocopies the patient phenotype and will serve as an important animal model for studies seeking therapeutic treatments for the resulting debilitating disease moving forward.

(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 authors undertake a detailed investigation focused on how the abundance of the sole Cav2 Ca2+ channel Cac in Drosophila is regulated at active zones (AZs) using the larval neuromuscular junction (NMJ) as a model system. The larval NMJ is a particularly powerful system to address this question, and the authors have taken full advantage of the unique approaches available. This work makes important advances in our understanding of AZ Ca2+ channel regulation during development and will be of significant interest to the field.

(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 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This study compares the roles of two interconnected dorsal pathway visual cortical areas, CIP and V3A, during perceptual decisions based on judging the tilt of 3D visual patterns. The potential impact of the paper stems from the novelty of directly comparing these two interconnected brain areas in perceptual decisions, and gives insight into their relative roles.

(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:

Punishment is key form of learning and behavior change, yet its core behavioral and brain mechanisms remain poorly understood and certainly less understood relative to reward learning. This manuscript uses dual fiber photometry to make an important advance in understanding how punishment is learned by studying how punishment changes action and punisher coding in the medial prefrontal cortex and ventral tegmental area of rats. The authors interpret the results as supporting a role for both areas in foraging in the face of risky outcomes. This work follows nicely on prior work and presents a straightforward and interesting experiment, using a validated anxiolytic to test what components of the neural response are related to this emotional component.

(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:

In this manuscript, the authors describe an inhibitory pathway from Purkinje cells in the cerebellum to a subset of molecular layer interneurons. The authors use in-vivo recordings to characterize these synaptic connections and probe their function during a delay conditioning task in vivo and using computer simulations. This is informative and an advance, but some claims regarding the function of this pathway need stronger substantiation. This is relevant to experimentalists and modelers interested in the cerebellum.

(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 seeks to expand our understanding of how spinally-projecting serotonergic neurons either inhibit or facilitate nociception depending on physiological context. Capitalizing on differential susceptibility to AAVretro transduction, the authors suggest identification of functional serotonergic subunits within the medullary raphe - one that includes innervation of the superficial dorsal horn and may modulate sensitivity to peripheral thermal stimuli, and another that includes innervation of a deeper lamina of the dorsal horn and may modulate sensitivity to mechanical von Frey stimulation. As well, the viral techniques and findings may inform the design and interpretation of work in the field.

(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 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary

This work aims to fill an important theoretical gap regarding the role of potential threats to the self in altruistic/prosocial helping. Much of the prevailing knowledge about the motivations for prosocial behavior focuses on the distress of the conspecific-in-need. Leveraging animal research, the authors hypothesize that defensive neural circuitry may aid prosocial helping under threat. Further building on prior work detailing responses along the threat imminence continuum, the authors hypothesize that cognitive fear circuits would respond to more distal threats whereas reactive fear circuits would respond to imminent threats. In addition to examining helping behavior under conditions of threat to self, the authors included representational similarity analyses (RSA) to examine how overlapping representations of self and other distress related to helping behavior. The potential to challenge existing empathy accounts of prosocial helping is intriguing and worthy of interrogation.

(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.)