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

Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington’s disease models DOI Creative Commons
Hongyu Zhang, Chun-Lei Zhang,

Jean Vincent

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Oct. 9, 2018

Abstract Impaired hippocampal synaptic plasticity contributes to cognitive impairment in Huntington’s disease (HD). However, the molecular basis of such defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that AMPAR surface diffusion, a key player plasticity, disturbed various rodent models HD. We demonstrate brain-derived neurotrophic factor (BDNF)–tyrosine receptor kinase B (TrkB) signaling pathway contribute deregulated trafficking by reducing interaction between transmembrane AMPA regulatory proteins (TARPs) PDZ-domain scaffold protein PSD95. The diffusion rescued antidepressant drug tianeptine via BDNF pathway. Tianeptine also restores impaired LTP hippocampus-dependent memory different HD mouse models. These findings unravel mechanism underlying dysfunction HD, highlight as promising therapeutic target.

Language: Английский

Citations

95
Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders DOI Creative Commons
Miranda Mele, Rui O. Costa, Carlos B. Duarte

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: March 7, 2019

GABAA receptors (GABAAR) are the major players in fast inhibitory neurotransmission central nervous system (CNS). Regulation of GABAAR trafficking and control their surface expression play important roles modulation strength synaptic inhibition. Different pieces evidence show that alterations distribution dysregulation turnover impair activity synapses. A diminished efficacy affects excitatory/inhibitory balance is a common feature various disorders CNS characterized by an increased excitability neuronal networks. The pool mainly controlled through regulation internalization, recycling lateral diffusion receptors. Under physiological condition these mechanisms finely coordinated to define GABAergic In this review article, we focus on alteration with impact function synapses CNS. particular discuss how similar molecular affecting consequently may be associated wide diversity pathologies CNS, from psychiatric acute leading death. better understanding cellular contribute impairment disorders, distribution, lead identification new pharmacological targets development novel therapeutic strategies.

Language: Английский

Citations

86
Species-conserved SYNGAP1 phenotypes associated with neurodevelopmental disorders DOI Creative Commons
Murat Kılınç,

Thomas K. Creson,

Camilo Rojas

et al.

Molecular and Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 91, P. 140 - 150

Published: March 24, 2018

Language: Английский

Citations

84
Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors DOI Creative Commons
Austin R Graves, Richard H. Roth, Han L. Tan

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Oct. 18, 2021

Elucidating how synaptic molecules such as AMPA receptors mediate neuronal communication and tracking their dynamic expression during behavior is crucial to understand cognition disease, but current technological barriers preclude large-scale exploration of molecular dynamics in vivo. We have developed a suite innovative methodologies that break through these barriers: new knockin mouse line with fluorescently tagged endogenous receptors, two-photon imaging hundreds thousands labeled synapses behaving mice, computer vision-based automatic synapse detection. Using tools, we can longitudinally track the strength populations changes behavior. used this approach generate an unprecedentedly detailed spatiotemporal map undergoing following sensory experience. More generally, tools be optical probe capable measuring functional across entire brain areas any behavioral paradigm, describing complex system-wide precision.

Language: Английский

Citations

64
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

Citations

58