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

CaMKII holoenzyme mechanisms that govern the LTP versus LTD decision DOI Creative Commons
Sarah G. Cook, Olivia R. Buonarati, Steven J. Coultrap

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(16)

Published: April 14, 2021

Molecular signal computation within the CaMKII holoenzyme determines direction of synaptic plasticity.

Language: Английский

Citations

57
Control of Synapse Structure and Function by Actin and Its Regulators DOI Creative Commons
Juliana E Gentile,

Melissa G Carrizales,

Anthony J. Koleske

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(4), P. 603 - 603

Published: Feb. 9, 2022

Neurons transmit and receive information at specialized junctions called synapses. Excitatory synapses form the junction between a presynaptic axon terminal postsynaptic dendritic spine. Supporting shape function of these is complex network actin filaments its regulators. Advances in microscopic techniques have enabled studies organization dynamic regulation. In addition to highlighting recent advances field, we will provide brief historical perspective understanding synaptic synapse. We also highlight key neuronal functions regulated by actin, including proteins pre- post- compartments endocytosis ion channels. review evidence that contain distinct pools differ their localization behaviors discuss for pools. Finally, whole exome sequencing humans with neurodevelopmental psychiatric disorders has identified regulators as disease risk genes. briefly summarize how genetic variants genes impact neurotransmission via on actin.

Language: Английский

Citations

49
Trafficking of NMDA receptors is essential for hippocampal synaptic plasticity and memory consolidation DOI
Xin Yang,

Ru Gong,

Linwei Qin

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 40(7), P. 111217 - 111217

Published: Aug. 1, 2022

Language: Английский

Citations

39
Tuning synaptic strength by regulation of AMPA glutamate receptor localization DOI Creative Commons
Imogen Stockwell, Jake F. Watson, Ingo H. Greger

et al.

BioEssays, Journal Year: 2024, Volume and Issue: 46(7)

Published: May 1, 2024

Abstract Long‐term potentiation (LTP) of excitatory synapses is a leading model to explain the concept information storage in brain. Multiple mechanisms contribute LTP, but central amongst them an increased sensitivity postsynaptic membrane neurotransmitter release. This predominantly determined by abundance and localization AMPA‐type glutamate receptors (AMPARs). A combination AMPAR structural data, super‐resolution imaging synapses, electrophysiological studies are providing ever‐clearer picture how AMPARs recruited organized at synaptic junctions. Here, we review latest insights into this process, discuss both cytoplasmic extracellular receptor elements cooperate tune response hippocampal CA1 synapse.

Language: Английский

Citations

12
A Presynaptic Perspective on Transport and Assembly Mechanisms for Synapse Formation DOI Creative Commons
Filiz Sila Rizalar, Dorien A. Roosen, Volker Haucke

et al.

Neuron, Journal Year: 2020, Volume and Issue: 109(1), P. 27 - 41

Published: Oct. 23, 2020

Language: Английский

Citations

56
The Role of ADF/Cofilin in Synaptic Physiology and Alzheimer’s Disease DOI Creative Commons

Youssif Ben Zablah,

Neil Merovitch, Zhengping Jia

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Nov. 12, 2020

ADF/cofilin, a family of actin-binding proteins, are critical for the regulation actin reorganization in response to various signals. Accumulating evidence indicates that ADF/cofilin also play important roles neuronal structure and function, including long-term potentiation depression. These most extensively studied forms long-lasting synaptic plasticity widely regarded as cellular mechanisms underlying learning memory. regulate function through their effects on dendritic spines trafficking glutamate receptors, principal mediator excitatory transmission vertebrates. Regulation involves signaling pathways converging LIM domain kinases slingshot phosphatases, which phosphorylate/inactivate dephosphorylate/activate respectively. activity is regulated by other activity-dependent subcellular distribution protein translation. Abnormalities have been associated with several neurodegenerative disorders such Alzheimer's disease. Therefore, investigating brain not only understanding fundamental processes governing but may provide potential therapeutic strategies treat disorders.

Language: Английский

Citations

54
Super-resolution microscopy: a closer look at synaptic dysfunction in Alzheimer disease DOI
Pranesh Padmanabhan, Andrew Kneynsberg, Jürgen Götz

et al.

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(12), P. 723 - 740

Published: Nov. 1, 2021

Language: Английский

Citations

46
Synaptic genes and neurodevelopmental disorders: From molecular mechanisms to developmental strategies of behavioral testing DOI Creative Commons
Caterina Michetti, Antonio Falace, Fabio Benfenati

et al.

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 173, P. 105856 - 105856

Published: Sept. 6, 2022

Synaptopathies are a class of neurodevelopmental disorders caused by modification in genes coding for synaptic proteins. These proteins oversee the process neurotransmission, mainly controlling fusion and recycling vesicles at presynaptic terminal, expression localization receptors postsynapse coupling between pre- postsynaptic compartments. Murine models, with homozygous or heterozygous deletion several knock-in specific pathogenic mutations, have been developed. They proved to be extremely informative understanding physiology, as well clarifying patho-mechanisms leading developmental delay, epilepsy motor, cognitive social impairments that most common clinical manifestations disorders. However, onset these emerges during infancy adolescence while behavioral phenotyping is often conducted adult mice, missing important information about impact development maturation on manifestation phenotype. Here, we review main achievements obtained testing murine models synaptopathies propose battery tests improve classification, diagnosis efficacy potential therapeutic treatments. Our aim underlie importance studying better focusing disease phenotypes.

Language: Английский

Citations

31
Neuroligin-3 confines AMPA receptors into nanoclusters, thereby controlling synaptic strength at the calyx of Held synapses DOI Creative Commons
Ying Han, Ran Cao, Liming Qin

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(24)

Published: June 15, 2022

The subsynaptic organization of postsynaptic neurotransmitter receptors into nanoclusters that are aligned with presynaptic release sites is essential for the high fidelity synaptic transmission. However, mechanisms controlling nanoscale in vivo remain incompletely understood. Here, we deconstructed role neuroligin-3 (Nlgn3), a adhesion molecule linked to autism, organizing AMPA-type glutamate calyx Held synapse. Deletion

Language: Английский

Citations

29
High-resolution imaging and manipulation of endogenous AMPA receptor surface mobility during synaptic plasticity and learning DOI Creative Commons
Angela M. Getz, Mathieu Ducros,

Christelle Breillat

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(30)

Published: July 27, 2022

Regulation of synaptic neurotransmitter receptor content is a fundamental mechanism for tuning efficacy during experience-dependent plasticity and behavioral adaptation. However, experimental approaches to track modify movements in integrated systems are limited. Exploiting AMPA-type glutamate receptors (AMPARs) as model, we generated knock-in mouse expressing the biotin acceptor peptide (AP) tag on GluA2 extracellular N-terminal. Cell-specific introduction ligase allows use monovalent or tetravalent avidin variants respectively monitor manipulate surface mobility endogenous AMPAR containing biotinylated AP-GluA2 neuronal subsets. immobilization precluded expression long-term potentiation formation contextual fear memory, allowing target-specific control animal behavior. The AP model offers unprecedented access resolve spatiotemporal dynamics receptors, opens new avenues study molecular mechanisms learning.

Language: Английский

Citations

29