Hippocampal Lactate-Infusion Enhances Spatial Memory Correlated with Monocarboxylate Transporter 2 and Lactylation DOI Creative Commons
Yuhan Wu, Hui Hu, Weiwei Liu

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(4), P. 327 - 327

Published: March 28, 2024

Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function an energy substrate signal molecule, recent research revealed lactate to serve epigenetic regulator the brain. However, molecular mechanisms by which regulates spatial memory role prevention of disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into mouse’s hippocampus, followed Morris water maze (MWM) test analyses. Improved performances were observed mice with lactate. Besides, upregulated expression synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), growth associated protein 43 (GAP43) hippocampal tissues HT22 cells, suggesting potential transmission formation. The facilitative monocarboxylate transporter 2 (MCT2), neuron-specific transporter, this process was confirmed, MCT2 antagonists attenuated lactate-induced upregulation proteins. Moreover, induced lactylation, post-translational modification, could be suppressed inhibition. RNA sequencing lactated-injected comprehensive gene profile influenced lactate, significant changes genes transcriptional progress. These data demonstrate that injection enhances mice, potentially through induction playing crucial these Our findings shed light on multi-faceted regulation, opening new avenues therapeutic interventions targeting disorders.

Language: Английский

NMDA receptor functions in health and disease: Old actor, new dimensions DOI Creative Commons
Julien P. Dupuis, Olivier Nicole, Laurent Groc

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(15), P. 2312 - 2328

Published: May 25, 2023

Language: Английский

Citations

66
Synaptic memory and CaMKII DOI Creative Commons
Roger A. Nicoll, Howard Schulman

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2897 - 2945

Published: June 8, 2023

Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and long-term potentiation (LTP) were discovered within a decade of each other have been inextricably intertwined ever since. However, like many marriages, it has had its up downs. Based on the unique biochemical properties CaMKII, was proposed as memory molecule before any physiological linkage made to LTP. reviewed here, convincing CaMKII synaptic physiology behavior took decades. New technologies critical in this journey, including vitro brain slices, mouse genetics, single-cell molecular pharmacological reagents, structure, two-photon microscopy, new investigators attracted by exciting challenge. This review tracks journey assesses state marriage 40 years on. The collective literature impels us propose relatively simple model for involving following steps that drive process: 1) entry through N-methyl-d-aspartate (NMDA) receptors activates CaMKII. 2) undergoes autophosphorylation resulting constitutive, -independent activity exposure binding site NMDA receptor subunit GluN2B. 3) Active translocates postsynaptic density (PSD) binds cytoplasmic C-tail 4) CaMKII-GluN2B complex initiates structural rearrangement PSD may involve liquid-liquid phase separation. 5) involves PSD-95 scaffolding protein, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPARs), their transmembrane AMPAR-regulatory (TARP) auxiliary subunits, an accumulation AMPARs underlies potentiation. 6) stability modified is maintained complex. 7) By process exchange or interholoenzyme phosphorylation maintains face turnover. There are important proteins participate enlargement spine modulation maintain In we critically discuss data underlying steps. As will become clear, some these more firmly grounded than others, provide suggestions how evidence supporting can be strengthened or, based data, replaced. Although long one, prospect having detailed cellular understanding learning at hand.

Language: Английский

Citations

55
Optoelectronic Synapses Based on MXene/Violet Phosphorus van der Waals Heterojunctions for Visual-Olfactory Crossmodal Perception DOI Creative Commons
Hailong Ma, Huajing Fang, Xinxing Xie

et al.

Nano-Micro Letters, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 1, 2024

The crossmodal interaction of different senses, which is an important basis for learning and memory in the human brain, highly desired to be mimicked at device level developing neuromorphic perception, but related researches are scarce. Here, we demonstrate optoelectronic synapse vision-olfactory perception based on MXene/violet phosphorus (VP) van der Waals heterojunctions. Benefiting from efficient separation transport photogenerated carriers facilitated by conductive MXene, photoelectric responsivity VP dramatically enhanced 7 orders magnitude, reaching up 7.7 A W

Language: Английский

Citations

29
Bioorthogonal chemical labeling of endogenous neurotransmitter receptors in living mouse brains DOI Creative Commons
Hiroshi Nonaka, Seiji Sakamoto,

Kazuki Shiraiwa

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(6)

Published: Jan. 31, 2024

Neurotransmitter receptors are essential components of synapses for communication between neurons in the brain. Because spatiotemporal expression profiles and dynamics neurotransmitter involved many functions delicately governed brain, vivo research tools with high resolution intact brains highly desirable. Covalent labeling by chemical reaction (chemical labeling) proteins without genetic manipulation is now a powerful method analyzing vitro. However, selective target receptor brain has not yet been achieved. This study shows that ligand-directed alkoxyacylimidazole (LDAI) chemistry can be used to selectively tether synthetic probes endogenous living mouse brains. The reactive LDAI reagents negative charges were found diffuse well over whole could label receptors, including AMPAR, NMDAR, mGlu1, GABA A R. simple robust protocol was then various applications: three-dimensional spatial mapping healthy disease-model mice; multi-color imaging; pulse–chase analysis postnatal Here, results demonstrated bioorthogonal modification animal may provide innovative molecular contribute in-depth understanding complicated functions.

Language: Английский

Citations

18
Advanced imaging and labelling methods to decipher brain cell organization and function DOI
Daniel Choquet, Matthieu Sainlos, Jean‐Baptiste Sibarita

et al.

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(4), P. 237 - 255

Published: March 12, 2021

Language: Английский

Citations

95
NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95 DOI Creative Commons
Benjamin Compans, Côme Camus,

Emmanouela Kallergi

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 14, 2021

Long-term depression (LTD) of synaptic strength can take multiple forms and contribute to circuit remodeling, memory encoding or erasure. The generic term LTD encompasses various induction pathways, including activation NMDA, mGlu P2X receptors. However, the associated specific molecular mechanisms effects on physiology are still unclear. We here compare how NMDAR- P2XR-dependent affect nanoscale organization function in rodents. While both LTDs with a loss reorganization AMPARs, only NMDAR-dependent triggers profound PSD-95. This modification, which requires autophagy machinery remove T19-phosphorylated form PSD-95 from synapses, leads an increase AMPAR surface mobility. demonstrate that these post-synaptic changes occur specifically during result increased short-term plasticity improving neuronal responsiveness depressed synapses. Our results establish P2XR- NMDAR-mediated functionally distinct LTD.

Language: Английский

Citations

85
Arc/Arg3.1 function in long‐term synaptic plasticity: Emerging mechanisms and unresolved issues DOI
Hongyu Zhang, Clive R. Bramham

European Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 54(8), P. 6696 - 6712

Published: Sept. 5, 2020

Abstract Arc (activity‐regulated cytoskeleton‐associated protein) is posited as a critical regulator of long‐term synaptic plasticity at excitatory synapses, including potentiation, depression, inverse tagging and homoeostatic scaling, with pivotal roles in memory postnatal cortical development. However, the mechanisms underlying bidirectional regulation strength are poorly understood. Here we review evidence from different paradigms, highlight outstanding issues discuss stimulus‐specific that dictate function. We propose model which bidirectionally controls by coordinate AMPA‐type glutamate receptor (AMPAR) trafficking actin cytoskeletal dynamics dendritic spines. Key to this model, proposed function an activity‐dependent AMPAR lateral membrane diffusion trapping synapses.

Language: Английский

Citations

76
Subsynaptic positioning of AMPARs by LRRTM2 controls synaptic strength DOI Creative Commons
Austin M. Ramsey, Ai‐Hui Tang, Tara A. LeGates

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(34)

Published: Aug. 20, 2021

The nanoscale distribution of AMPA receptors is under rapid control by adhesion proteins and helps regulate their activation.

Language: Английский

Citations

67
Molecular Pathophysiological Mechanisms in Huntington’s Disease DOI Creative Commons
Anamaria Jurcău

Biomedicines, Journal Year: 2022, Volume and Issue: 10(6), P. 1432 - 1432

Published: June 17, 2022

Huntington's disease is an inherited neurodegenerative described 150 years ago by George Huntington. The genetic defect was identified in 1993 to be expanded CAG repeat on exon 1 of the huntingtin gene located chromosome 4. In following almost 30 years, a considerable amount research, using mainly animal models or vitro experiments, has tried unravel complex molecular cascades through which transcription mutant protein leads neuronal loss, especially medium spiny neurons striatum, and excitotoxicity, transcriptional dysregulation, mitochondrial dysfunction, oxidative stress, impaired proteostasis, altered axonal trafficking reduced availability trophic factors crucial contributors. This review discusses pathogenic literature demise. However, due ubiquitous presence huntingtin, astrocytes are also dysfunctional, neuroinflammation may additionally contribute pathology. quest for therapies delay onset reduce rate progression ongoing, but based findings from basic research.

Language: Английский

Citations

63
Bioorthogonal labeling of transmembrane proteins with non-canonical amino acids unveils masked epitopes in live neurons DOI Creative Commons
Diogo Bessa‐Neto, Gerti Beliu, Alexander Kuhlemann

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 18, 2021

Progress in biological imaging is intrinsically linked to advances labeling methods. The explosion the development of high-resolution and super-resolution calls for new approaches label targets with small probes. These should allow faithfully report localization target within resolution - typically nowadays a few nanometers access any epitope target, native cellular tissue environment. We here complete pipeline using genetic code expansion non-canonical amino acids neurons that allows fluorescently masked epitopes transmembrane proteins live neurons, both dissociated culture organotypic brain slices. This us image differential two AMPA receptor (AMPAR) auxiliary subunits AMPAR regulatory protein family complex their partner variety methods including widefield, confocal, dSTORM microscopy.

Language: Английский

Citations

58