Quantitative Nano‐amperometric Measurement of Intravesicular Glutamate Content and its Sub‐Quantal Release by Living Neurons DOI

Xiaoke Yang,

Fuli Zhang, Wentao Wu

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(29), P. 15803 - 15808

Published: April 30, 2021

Abstract Quantitative measurements of intravesicular glutamate (Glu) and transient exocytotic release contents directly from individual living neurons are highly desired for understanding the mechanisms (full or sub‐quantal release?) synaptic transmission plasticity. However, this could not be achieved so far due to lack adequate experimental strategies relying on selective sensitive Glu nanosensors. Herein, we introduce a novel electrochemical nanobiosensor based single SiC nanowire that can selectively measure in real‐time fluxes released via exocytosis by large vesicles (ca. 125 nm diameter) present hippocampal axonal varicosities as well their content before exocytosis. These revealed mode neurons, viz., only ca. one third half molecules during events. Importantly, fraction remained practically same when were pretreated with L‐Glu‐precursor L‐glutamine, while it significantly increased after zinc treatment, although both cases drastically affected.

Language: Английский

A trans-synaptic nanocolumn aligns neurotransmitter release to receptors DOI
Ai‐Hui Tang, Haiwen Chen, Tuo Peter Li

et al.

Nature, Journal Year: 2016, Volume and Issue: 536(7615), P. 210 - 214

Published: July 26, 2016

Language: Английский

Citations

621

Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert DOI Creative Commons
Andreas Reiner, Joshua Levitz

Neuron, Journal Year: 2018, Volume and Issue: 98(6), P. 1080 - 1098

Published: June 1, 2018

Language: Английский

Citations

507

Cerebral plasticity: Windows of opportunity in the developing brain DOI
Fatima Ismail, Ali Fatemi, Michael V. Johnston

et al.

European Journal of Paediatric Neurology, Journal Year: 2016, Volume and Issue: 21(1), P. 23 - 48

Published: Aug. 10, 2016

Language: Английский

Citations

455

Excitation/Inhibition Imbalance in Animal Models of Autism Spectrum Disorders DOI Creative Commons
Eunee Lee, Jiseok Lee, Eunjoon Kim

et al.

Biological Psychiatry, Journal Year: 2016, Volume and Issue: 81(10), P. 838 - 847

Published: May 22, 2016

Imbalances between excitation and inhibition in synaptic transmission neural circuits have been implicated autism spectrum disorders. Excitation imbalances are frequently observed animal models of disorders, their correction normalizes key autistic-like phenotypes these animals. These results suggest that may contribute to the development maintenance disorders represent an important therapeutic target.

Language: Английский

Citations

434

Long-Term Potentiation: From CaMKII to AMPA Receptor Trafficking DOI
Bruce E. Herring, Roger A. Nicoll

Annual Review of Physiology, Journal Year: 2016, Volume and Issue: 78(1), P. 351 - 365

Published: Feb. 10, 2016

For more than 20 years, we have known that Ca 2+ /calmodulin-dependent protein kinase (CaMKII) activation is both necessary and sufficient for the induction of long-term potentiation (LTP). During this time, tremendous effort has been spent in attempting to understand how CaMKII gives rise phenomenon. Despite such efforts, there much be learned about molecular mechanisms involved LTP downstream activation. In review, highlight recent developments shaped our current thinking underlying discuss important questions remain field.

Language: Английский

Citations

407

Identification of an elaborate complex mediating postsynaptic inhibition DOI Open Access
Akiyoshi Uezu, Daniel J. Kanak, Tyler WA Bradshaw

et al.

Science, Journal Year: 2016, Volume and Issue: 353(6304), P. 1123 - 1129

Published: Sept. 8, 2016

Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. The composition of the inhibitory postsynapse and mechanistic basis its regulation, however, remain poorly understood. We used an in vivo chemico-genetic proximity-labeling approach to discover proteins. Quantitative mass spectrometry not only recapitulated known proteins but also revealed a large network new proteins, many which are either implicated neurodevelopmental disorders or unknown function. Clustered regularly interspaced short palindromic repeats (CRISPR) depletion one these previously uncharacterized InSyn1, led decreased sites, reduced frequency miniature currents, increased excitability hippocampus. Our findings uncover rich functionally diverse assemblage that regulate inhibition might contribute developmental brain disorders.

Language: Английский

Citations

345

Let’s call the whole thing off: evaluating gender and sex differences in executive function DOI Open Access
Nicola M. Grissom, Teresa M. Reyes

Neuropsychopharmacology, Journal Year: 2018, Volume and Issue: 44(1), P. 86 - 96

Published: Aug. 14, 2018

Language: Английский

Citations

230

Linking glutamate receptor movements and synapse function DOI Open Access
Laurent Groc, Daniel Choquet

Science, Journal Year: 2020, Volume and Issue: 368(6496)

Published: June 11, 2020

Receptors moving in and out of the synapse The number neurotransmitter receptors their spatial organization on postsynaptic site is a central determinant synaptic efficacy. Sophisticated techniques to visualize track movement single molecules have provided us with profound new insights into these dynamics. We now know that undergo movements different scales. Groc Choquet review our present understanding mechanisms regulate glutamate receptor localization clustering. Receptor are fundamental basic function participate many forms plasticity. Science , this issue p. eaay4631

Language: Английский

Citations

184

Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications DOI Creative Commons

Chen-Chen Jiang,

Lishan Lin,

Sen Long

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 11, 2022

Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental which has strong genetic basis. Despite the rapidly rising incidence of autism, little known about its aetiology, risk factors, disease progression. There are currently neither validated biomarkers for diagnostic screening nor specific medication autism. Over last two decades, there have been remarkable advances in genetics, with hundreds genes identified as being associated high The convergence neuroscience methods becoming more widely recognized significance elucidating pathological mechanisms Efforts devoted to exploring behavioural functions, key potential treatments Here, we highlight this review, emerging evidence shows that signal transduction molecular events involved processes such transcription, translation, synaptic transmission, epigenetics immunoinflammatory responses. This involvement important implications discovery precise targets Moreover, review recent insights into clinical autism from molecular, cellular, neural circuit, neurobehavioural aspects. Finally, challenges future perspectives discussed regard novel strategies predicated on biological features

Language: Английский

Citations

133

The neuronal pentraxin Nptx2 regulates complement activity and restrains microglia-mediated synapse loss in neurodegeneration DOI
Jiechao Zhou, Sarah D. Wade, David Graykowski

et al.

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(689)

Published: March 29, 2023

Complement overactivation mediates microglial synapse elimination in neurological diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD), but how complement activity is regulated the brain remains largely unknown. We identified that secreted neuronal pentraxin Nptx2 binds C1q thereby regulates its brain. Nptx2-deficient mice show increased activity, C1q-dependent engulfment, loss of excitatory synapses. In a neuroinflammation culture model aged TauP301S mice, adeno-associated virus (AAV)–mediated overexpression was sufficient to restrain ameliorate microglia-mediated loss. Analysis human cerebrospinal fluid (CSF) samples from genetic FTD cohort revealed reduced concentrations Nptx2-C1q protein complexes symptomatic patients, which correlated with elevated activated C3. Together, these results diminished might exacerbate complement-mediated neurodegeneration patients FTD.

Language: Английский

Citations

68