Neuroscience

APP β-CTF triggers cell-autonomous synaptic toxicity independent of Aβ

1. Mengxun Luo
2. Jia Zhou
3. Cailu Sun
4. Wanjia Chen
5. Chaoying Fu
6. Chenfang Si
7. Yaoyang Zhang
8. Yang Geng
9. Yelin Chen

• Curated by eLife

  eLife Assessment

  This study presents a useful demonstration that a specific protein fragment may induce the loss of synapses in Alzheimer's disease. The evidence supporting the data is solid but only partially supports the conclusion and would benefit from additional discussion indicated by the literature from reviewer #1. The application of the findings is limited because blocking the formation of the protein fragment has not benefited patients in several clinical trials.

Reviewed by eLife

Neural mechanisms of credit assignment for delayed outcomes during contingent learning

1. Phillip P Witkowski
2. Lindsay JH Rondot
3. Zeb Kurth-Nelson
4. Mona M Garvert
5. Raymond J Dolan
6. Timothy EJ Behrens
7. Erie Boorman

• Curated by eLife

  eLife Assessment

  This study provides important findings that during credit assignment, the lateral orbitofrontal cortex (lOFC) and hippocampus (HC) encode causal choice representations, while the frontopolar cortex (FPl) mediates HC -lOFC interactions when the causality needs to be maintained over longer distractions. This research offers compelling evidence and employs sophisticated multivariate pattern analysis. However, while the task design captures the delayed component, it lacks the full complexity and ambiguity of the credit assignment process observed in real-world scenarios. Moreover, the data indicated that other frontal regions beyond just lOFC were involved in delayed credit assignment. This work will be of interest to cognitive and computational neuroscientists who work on value-based decision-making and fronto-hippocampal circuits.

Reviewed by eLife

Microglia from patients with multiple sclerosis display a cell-autonomous immune activation state

1. Tanja Hyvärinen
2. Johanna Lotila
3. Luca Giudice
4. Iisa Tujula
5. Marjo Nylund
6. Sohvi Ohtonen
7. Flavia Scoyni
8. Henna Jäntti
9. Sara Pihlava
10. Heli Skottman
11. Susanna Narkilahti
12. Laura Airas
13. Tarja Malm
14. Sanna Hagman

Reviewed by PREreview

Repeated activation of preoptic area recipient neurons in posterior paraventricular nucleus mediates chronic heat-induced negative emotional valence and hyperarousal states

1. Zhiping Cao
2. Wing-Ho Yung
3. Ya Ke

• Curated by eLife

  eLife Assessment

  This important study identifies one way in which episodic heat exposure can result in negative changes in motivated and affective behaviors. This work positively expands the field of thermoregulation. The data were collected using a myriad of next-generation approaches, including extensive behavior testing, thermal monitoring, electrophysiology, circuit mapping, and manipulations. There is convincing evidence that neurons of the paraventricular thalamus change plastically over three weeks of episodic heat stimulation this affects behavioral outputs such as social interactions and anxiety-related behavior. Conclusions regarding the specificity of the POA-pPVT pathway compared to other inputs to the PVT in the control of observed effects would benefit from further validation. The study will be of interest to behavioral neuroscientists, climate/environmental biologists, and pre-clinical neuropsychiatrists.

Reviewed by eLife

Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2G2019S model of Parkinson’s disease

1. Zachary Gaertner
2. Cameron Oram
3. Amanda Schneeweis
4. Elan Schonfeld
5. Cyril Bolduc
6. Chuyu Chen
7. Daniel Dombeck
8. Loukia Parisiadou
9. Jean-Francois Poulin
10. Rajeshwar Awatramani

• Curated by eLife

  eLife Assessment

  This important study combines single nucleus transcriptional profiling with spatial transcriptomics to identify and map heterogeneity among dopamine neurons in the mouse ventral midbrain. The compelling results separate dopamine neurons into three broad families that have unique (yet overlapping) spatial distribution within the ventral tegmental area and substantia nigra, and also identify population-specific changes in a LRRK2 mouse model of Parkinson's Disease. The creation of a public-facing app where the snRNA-seq data can be investigated by anyone is a major strength.

Reviewed by eLife

Layer 6 corticocortical neurons are a major route for intra- and interhemispheric feedback

1. Simon Weiler
2. Manuel Teichert
3. Troy W Margrie

• Curated by eLife

  eLife Assessment

  This important study compares the cortical projections to primary motor and sensory areas originating from the ipsilateral and contralateral hemispheres. Results show that, while there is substantial symmetry between the two hemispheres regarding the areas sending projections to these primary cortical areas, contra-hemispheric projections had more inputs from layer 6 neurons than ipsi-projecting ones. The evidence is compelling and the conclusions are supported by rigorous analyses.

Reviewed by eLife

The asymmetric transfers of visual perceptual learning determined by the stability of geometrical invariants

1. Yan Yang
2. Yan Zhuo
3. Zhentao Zuo
4. Tiangang Zhuo
5. Lin Chen

• Curated by eLife

  eLife Assessment

  This important and unique study proposes a framework to understand and predict generalization in visual perceptual learning in humans based on form invariants. Using behavioral experiments in humans and by training deep networks, the authors offer evidence that the presence of stable invariants in a task leads to faster learning. However, this interpretation is promising but counter-intuitive and incomplete, since there could be possible other confounds such as differing attentional demands that lead to differing patterns of generalization. It can be strengthened through additional experiments and by rejecting alternate explanations.

Reviewed by eLife

Efficient coding explains neural response homeostasis and stimulus-specific adaptation

1. Edward James Young
2. Yashar Ahmadian

• Curated by eLife

  eLife Assessment

  This work derives a valuable general theory unifying theories of efficient information transmission in the brain with population homeostasis. The general theory provides an explanation for firing rate homeostasis at the level of neural clusters with firing rate heterogeneity within clusters. Applying this theory to the primary visual cortex, the authors present solid evidence that accounts for stimulus-specific and neuron-specific adaptation.

Reviewed by eLife

Modulation of habenula axon terminals supports action-outcome associations in larval zebrafish

1. Emanuele Paoli
2. Virginia Palieri
3. Amey Shenoy
4. Ruben Portugues

Reviewed by preLights

Distinct representational properties of cues and contexts shape fear learning and extinction

1. Antoine Bouyeure
2. Daniel Pacheco
3. Marie-Christin Fellner
4. George Jacob
5. Malte Kobelt
6. Jonas Rose
7. Nikolai Axmacher

• Curated by eLife

  eLife Assessment

  This is an important study with solid evidence that multi-voxel fMRI activity patterns for threat-conditioned stimuli are altered by learning CS-US contingencies. The analyses are dense but mostly rigorous. The protocol is quite nuanced and complex, but the authors have done a fair job of explaining and presenting the results, and the results could be further improved by adjustment for multiple comparisons. The readability could be improved for an audience without highly-specialised knowledge of the field and the fMRI analytical approach.

Reviewed by eLife