Neuroscience

Evaluation Summary:

Using advanced live brain imaging techniques, the authors studied the activities of neurons in the primary motor cortex of mice during a classical conditional task, in which a tone is paired with water reward. They found that distinct types of neurons respond differently to the auditory cue or the reward, and the responses evolve differentially as learning proceeds. This work reveals an interesting role of the motor cortex beyond its well-recognized function in motor control, and suggests distinct functions of pyramidal neurons as well as various interneurons in reinforcement 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. Reviewer #1 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript examines how effort is integrated into economic decisions by recording neural activity from the dorsal anterior cingulate cortex (ACC) in monkeys, while requiring animals to choose between different juice types offered in variable amounts and with different action costs. The ACC is a relevant area because some theories have suggested it is important for evaluating or selecting among potential actions during decision-making, although evidence supporting this idea has been inconsistent. The main results provide evidence against the notion that ACC contributes to evaluation of potential actions. Instead, neurons predominantly coded for post-decision variables, such as cost of the chosen target and the juice type of the chosen offer, but not pre-decision variables, such as offer values. This is in contrast to OFC encoding in the same task (and same subjects), in which neurons encoded the effort associated with choice options. The authors conclude that ACC is unique in representing more post-decision variables than OFC, and in its encoding of outcomes in several reference frames (chosen juice, chosen cost, and chosen action). Together, the results are convincing and highlight potentially unique roles of ACC neurons in learning and decision making.

(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 explores the mechanism of vacor toxicity in neurons. The authors provide exciting and definitive data that vacor drives neurodegeneration by direct binding and activation of SARM1, a potent regulator of axon death. The work elucidates the vacor mechanism of action, provides strong in vitro and in vivo data that toxicity is entirely dependent on SARM1, and will advance the field in terms of how we understand vacor-induced toxicity, and provides a new model for testing anti-SARM1 therapeutics.

(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 names with the authors.)

Evaluation Summary:

This is a rigorous study that confirms the existence of functional KATP and dominant oxidative metabolism in several types of juvenile somatosensory cortical neurons. The authors present multiple lines of experimental results examining the effects of lactate on neocortical neuron types. They also report a mechanism by which lactate is likely to enhance neuronal firing. The data is convincing in supporting the conclusions in the manuscript.

(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 manuscript adds to an emerging story about the role of activity in the formation of callosal connections across the brain. Previous research of the authors' and other labs had shown that overexpressing the potassium channel Kir2.1, which reduces activity levels in the developing cortical network, blocks the formation of callosal connections almost entirely. Here, the authors show that they can use a TET system to switch off the activity of an Kir2.1 to probe when activity might be necessary or sufficient for the formation of callosal connections. The authors find that artificial restoration of activity with DREADS is sufficient to rescue the formation of callosal connections, and that there is a critical period (somewhere between P5-P15) where activity must occur in order for the connections to form within the cortex. Finally, the authors show that when the potassium channel is removed during the critical period, the cortex exhibits activity, but few highly synchronous events. These results indicate that it is activity in general and not specifically highly synchronous activity that is necessary for the final innervation of the callosal cortex.

(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 names with the authors.)

Evaluation Summary:

Mulholland et al show that there is a very close relationship between the development of excitatory and inhibitory networks in the developing cortex. This paper makes an important contribution to our understanding of the structure of inhibition during an early stage in cortical development. It is therefore of great interest to scientists interested in development, and in computation in cortical circuits. The work has been carefully performed and analysed.

(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 study uses a novel rodent surgical model for establishing that dual nerve transfer in the upper extremity improves neuromuscular regeneration in comparison to single nerve transfer. The authors provide a detailed description of how the model is developed and they characterize neuromuscular regeneration through nerve crush, neurotomy, behavioral analysis, and retrograde labeling. The nerve transfer method is clearly delineated for researchers to use in future scientific and clinical applications. The evidence clearly support the main study conclusions. Thus, this manuscript is of great interest to readers in the field of peripheral nerve repair and neural interfaces.

(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:

By combining real-time closed-loop EEG-TMS and computational modelling, this study ambitiously examined the causal role of prefrontal cortex in resolving perceptual ambiguity. It impressively demonstrates brain-state-dependent effects on bistable perception.

(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 presents and evaluates a machine learning method for segmenting and annotating animal acoustic communication signals. The paper presents results from applying the method to signals from Drosophila, mice, and songbirds, but the method should be useful for a broad range of researchers who record animal vocalizations. The method appears to be easily generalizable and has high throughput and modest training times.

(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 names with the authors.)

Evaluation Summary:

This study recorded brain activity in monkeys to identify the neural mechanisms underlying an attention-related scalp ERP component that is similar to the human N2pc component. Intriguing evidence was provided that the surface potential was at least partly a result of current flows in the feedback-receiving supragranular and infragranular layers of area V4, not the granular layer that receives feedforward inputs. However, it is not entirely clear if these very interesting intracortical effects are the source of the scalp ERP effects.

(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 names with the authors.)