Neuroscience

Evaluation Summary:

Han et al. report the discovery of an amino acid transporter that is required locally at axon terminals of fly photoreceptors neurons for the uptake of histidine, the precursor of the neurotransmitter histamine. This function is required for transmitter synthesis locally and neurotransmission. The work exemplifies a specialized model for local monoamine transmitter synthesis at synapses in the nervous system, the generality of which for other monoamine systems remains to be tested.

(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:

Lövestam et al. report 76 cryo-EM structures of in vitro assembled recombinant tau filaments, including 27 previously unobserved ones. Together with the recent paper from Scheres and Goedert research groups, the structure-based knowledge of amyloid assembly will be boosted several fold. Most importantly, a few in vitro conditions were found to replicate the amyloid structures from both Alzheimer's disease and chronic traumatic encephalopathy. Those findings will open up new avenues to quickly screen compounds that inhibit filament formation under in vitro conditions, as well as the (self-)assembly process of amyloid fibrils.

(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 #3 and Reviewer #4 agreed to share their name with the authors.)

Evaluation Summary:

The manuscript provides strong support for the concept that oligodendrocyte alterations contribute to neurological disorders that were previous thought to be primarily cell autonomous to neurons. The work is very well done, the results presented are clear and convincing, and the discussion is reasonable and interesting. The study will have considerable impact on the assessment of various neurodegenerative disorders with TDP-43 alterations.

(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 of interest to the motor neuroscience, movement disorder, human electrophysiology, and brain computer interface communities. It examines the effectiveness of signals recorded from the subthalamic nucleus (STN) and along sensorimotor regions of the cortex for decoding simple movements in patients with Parkinson's disease. Additionally, a relationship between symptom severity and decoding performance is identified. With the recent advent of implantable closed-loop stimulators for neurological conditions such as Parkinson's disease, this paper addresses current knowledge gaps that may inform both surgical and engineering considerations for optimizing these new types of therapies.

(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 will be of interest people studying mechanosensation (particularly touch and pain sensation) and ion channels. The authors use a combination of electrophysiology and imaging to provide evidence that the force-gated ion channel Piezo2 is negatively regulation by the enzyme Tmem120A/Tacan. The results from the heterologous expression aspects of study are relatively robust and may have potential impact on the field. The physiological relevance of these findings await further investigation.

(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 addresses the cellular and dendritic physiology of cholinergic interneurons in the striatum. The authors use a creative integration of electrophysiology and optical methods to investigate this distinctive cell type, which is critically important at the intersection of motivated behavior and disease. They uncover a mechanism through which two separate active conductances - the hyperpolarization-activated h-current (HCN) and the persistent sodium current (NaP) - act in concert to selectively boost synaptic input from the thalamus onto proximal dendrites of cholinergic interneurons.

(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 demonstrate that patients carrying a gain-of-function S218L mutation in CACNA1A exhibit a gene-dosage-dependent increase in the susceptibility to cortical spreading depression (CSD), seizure activity and brain edema formation following TBI compared with wild-type (WT) mice or mice carrying the milder R192Q mutation. This paper will be of considerable interest to familial hemiplegic migraine (FHM) sufferers who experience traumatic brain injury (and their physicians), as well researchers with an interest in the spectrum and phenotypic consequences of mutations in the voltage-gated, P/Q-type Ca2+ channel, CACNA1A.

(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 phenomena of inter brain synchrony is fascinating and has been observed in a variety of situations across different mammalian species. It has also been proposed to play a critical role in certain social behaviors. Here, the authors report that brain activity across two interacting bats display not only similarities but also important differences.

(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 investigated Atmospheric Particulate Matter (PM) , a mimetic of current air pollution and how it affects myelination in the central nervous system (CNS) using an animal model of demyelination. They showed that the PM caused changes in myelination that associated with microglial activation and markers of inflammation. In vitro modeling indicates PM can activate microglial via the TLR4/NFkB signaling pathway.

(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 make a compelling case for a special type of potassium channel (Kv3.3) in the control of the presynaptic AP spike waveforms. Importantly, mice that lack Kv3.3 showed auditory response deficits, including increases in pre-synaptic AP halfwidth, AP latency, AP jitter and spontaneous activity. The in vivo recordings are impressive. The study contains an extensive data set and makes a compelling argument for the uniquely important role for Kv3.3 in synaptic transmission. Overall, the findings will significantly advance our understanding of the calyx of Held and the neural circuit of sound processing, as well as the functions of Kv3 channels.

(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.)