Neuroscience

The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system of daf-18/PTEN Caenorhabditis elegans mutants

1. Sebastián Giunti
2. María Gabriela Blanco
3. María José De Rosa
4. Diego Rayes

• Curated by eLife

  eLife assessment

  This is a conceptually appealing study in which the authors identify genes whose function is important for the development of inhibitory (GABA) neurons, and then demonstrate that a diet rich in ketone body β-hydroxybutyrate partially suppresses specific mutant phenotypes. The authors provide compelling evidence that features methods, data and analyses more rigorous than the current state-of-the-art. Conceptually, this is evidence of a rescue of a developmental defect with dietary metabolic intervention, linking, in an elegant way, the underpinning genetic mechanisms with novel metabolic pathways that could be used to circumvent the defects.

Reviewed by eLife

Key determinants of the dual clamp/activator function of Complexin

1. Mazen Makke
2. Alejandro Pastor-Ruiz
3. Antonio Yarzagaray
4. Surya Gaya
5. Michelle Zimmer
6. Walentina Frisch
7. Dieter Bruns

• Curated by eLife

  eLife assessment

  This important work shows compelling data that significantly advances our understanding of the regulation of neurotransmitter and hormone secretion by exploring the mechanisms of how the protein complexin 2 (Cplx2) interacts with the calcium sensor synaptotagmin. The function of mammalian Cplx2 is studied using chromaffin cells derived from Cplx2 knock out mice as a system to overexpress and functionally characterize mutant Cplx2 forms and the interaction between Cplx2 and synaptotagmin. The authors identify structural requirements within the protein for Cplx's dual role in preventing premature vesicle exocytosis and enhancing evoked exocytosis. The findings are of broad interest to neuroscientists and cell biologists.

Reviewed by eLife

Plural molecular and cellular mechanisms of pore domain KCNQ2 encephalopathy

1. Timothy J Abreo
2. Emma C Thompson
3. Anuraag Madabushi
4. Kristen L Park
5. Heun Soh
6. Nissi Varghese
7. Carlos G Vanoye
8. Kristen Springer
9. Jim Johnson
10. Scotty Sims
11. Zhigang Ji
12. Ana G Chavez
13. Miranda J Jankovic
14. Bereket Habte
15. Aamir R Zuberi
16. Cathleen M Lutz
17. Zhao Wang
18. Vaishnav Krishnan
19. Lisa Dudler
20. Stephanie Einsele-Scholz
21. Jeffrey L Noebels
22. Alfred L George
23. Atul Maheshwari
24. Anastasios Tzingounis
25. Edward C Cooper

• Curated by eLife

  eLife assessment

  The paper investigates a potential cause of a type of severe epilepsy that develops in early life because of a defect in a gene called KCNQ2. The significance is fundamental because it substantially advances our understanding of a major research question. The strength of the evidence is convincing because appropriate methods are used that are in line with the state-of-the art.

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Sequential Deactivation Across the Hippocampus‐Thalamus‐mPFC Pathway During Loss of Consciousness

1. Xiaoai Chen
2. Samuel R. Cramer
3. Dennis C.Y. Chan
4. Xu Han
5. Nanyin Zhang

Reviewed by PREreview

Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis

1. Luting Yang
2. Chunqing Hu
3. Xiaowen Chen
4. Jie Zhang
5. Zhe Feng
6. Yanxin Xiao
7. Weitai He
8. Tingting Cui
9. Xin Zhang
10. Yang Yang
11. Yaling Zhang
12. Yaping Yan

• Curated by eLife

  eLife assessment

  This important work describes the activation of astrocytes via the nuclear translocation of PKM2 in an animal model of multiple sclerosis. This study provides convincing evidence of the interaction between TRIM21 and PKM2 as the crucial molecular event leading to the translocation of PKM2 and a metabolic shift towards glycolysis dominance, fostering proliferation in stimulated astrocytes. This finding is significant as it underscores the potential of targeting glycolytic metabolism to mitigate neurological diseases mediated by astrocytes, offering a strong rationale for potential therapeutic interventions.

Reviewed by eLife

Laminar specificity and coverage of viral-mediated gene expression restricted to GABAergic interneurons and their parvalbumin subclass in marmoset primary visual cortex

1. Frederick Federer
2. Justin Balsor
3. Alexander Ingold
4. David P Babcock
5. Jordane Dimidschstein
6. Alessandra Angelucci

• Curated by eLife

  eLife assessment

  Unlocking the potential of molecular genetic tools (optogenetics, chemogenetics, sensors, etc.) for the study of systems neuroscience in nonhuman primates requires the development of effective regulatory elements for cell-type specific expression to facilitate circuit dissection. This study provides a valuable building block, by carefully characterizing the laminar expression profile of two optogenetic enhancers, one designed for general GABA+ergic neurons (h56D) and the second (S5E2) for parvalbumin+ cell-type selective expression in the marmoset primary visual cortex. This study contributes solid evidence to our understanding of these tools but is limited by the understandably small number of animals used.

Reviewed by eLife

Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

1. Felix Michaud
2. Ruggiero Francavilla
3. Dimitry Topolnik
4. Parisa Iloun
5. Suhel Tamboli
6. Frederic Calon
7. Lisa Topolnik

• Curated by eLife

  eLife assessment

  This study describes fundamental findings related to early disruptions in disinhibitory modulation exerted by VIP+ interneurons, in CA1 in a transgenic model of Alzheimer's disease pathology. The authors provide a compelling analysis at the cellular, synaptic, network, and behavioral levels on how these changes correlate and might be related to behavioral impairments during these early stages of AD pathology.

Reviewed by eLife

Associative plasticity of granule cell inputs to cerebellar Purkinje cells

1. Rossella Conti
2. Céline Auger

• Curated by eLife

  eLife assessment

  This study presents valuable findings on an unresolved question of cerebellar physiology: Do synapses between Purkinje cells and granule cells, made by the ascending part of the granule cells' axon, have different properties than those made by parallel fibers? The authors conducted patch-clamp recordings on rat cerebellar slices and found a new type of plasticity in the synapses of the ascending part of granule cell axons. The experiments are well-designed with appropriate controls, and the study provides solid evidence for the new form of cerebellar synaptic plasticity.

Reviewed by eLife

Distinct catecholaminergic pathways projecting to hippocampal CA1 transmit contrasting signals during navigation in familiar and novel environments

1. Chad Heer
2. Mark Sheffield

• Curated by eLife

  eLife assessment

  This study presents important findings on the differential activity of noradrenergic and dopaminergic input to dorsal hippocampus CA1 in head-fixed mice traversing a runway in a virtual environment that is familiar or novel. The data are rigorously analysed, and the observed divergence in the dynamics of activity in the dopaminergic and noradrenergic axons is solid. Future studies, using specific manipulations of the two distinct midbrain inputs combined with behavioral testing, are required to strengthen the claim that distinct signals to the hippocampus cause distinct behavioral effects.

Reviewed by eLife

Microprism-based two-photon imaging of the mouse inferior colliculus reveals novel organizational principles of the auditory midbrain

1. Baher A Ibrahim
2. Yoshitaka Shinagawa
3. Austin Douglas
4. Gang Xiao
5. Alexander R Asilador
6. Daniel A Llano

• Curated by eLife

  eLife assessment

  This study provides valuable new insights into how multisensory information is processed in the lateral cortex of the inferior colliculus, a poorly understood part of the auditory midbrain. By developing new imaging techniques that provide the first optical access to the lateral cortex in a living animal, the authors provide convincing in vivo evidence that this region contains separate subregions that can be distinguished by their sensory inputs and neurochemical profiles, as suggested by previous anatomical and in vitro studies. This work provides a foundation for future research exploring how this part of the auditory midbrain contributes to multisensory-based behavior.

Reviewed by eLife