Imaging Synaptic Glutamate Release with Two-Photon Microscopy in Organotypic Slice Cultures

Dürst, Céline D.; Oertner, Thomas G.

doi:10.1007/978-1-0716-1916-2_16

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…They can traffick into or near synaptic clefts to directly measure the timing and magnitude of neurotransmitter transients ( Helassa et al, 2018 ; Marvin et al, 2019 , 2013 ; Sabatini and Tian, 2020 ). With a 2-photon microscope, this approach can be used to resolve spatiotemporal concentration changes occurring at an individual synapse ( Dürst and Oertner, 2022 ), which is not feasible with the whole-cell recordings. Complications of measuring both transmitters using fluorescent sensors include compensating for differential sensitivity, binding kinetics, and bleaching rates, which may need to be addressed during the post-hoc analysis of these signals.…”

Section: Alternative Methods For Measuring Glutamate/gamma-aminobutyr...mentioning

confidence: 99%

Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging

Kim

Sabatini

2023

Front. Synaptic Neurosci.

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Multi-transmitter neurons, i.e., those that release more than one type of neurotransmitter, have been found in many organisms and brain areas. Given the peculiar biology of these cells, as well as the potential for diverse effects of each of the transmitters released, new tools, and approaches are necessary to parse the mechanisms and functions of synaptic co-transmission. Recently, we and others have studied neurons that project to the lateral habenula and release both gamma-aminobutyric acid (GABA) and glutamate, in some cases by packaging both transmitters in the same synaptic vesicles. Here, we discuss the main challenges with current electrophysiological approaches to studying the mechanisms of glutamate/GABA co-release, a novel statistical analysis that can identify co-packaging of neurotransmitters versus release from separate vesicle, and the implications of glutamate/GABA co-release for synapse function and plasticity.

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Section: Alternative Methods For Measuring Glutamate/gamma-aminobutyr...mentioning

confidence: 99%

Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging

Kim

Sabatini

2023

Front. Synaptic Neurosci.

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“…Application of Amyloid-β 1−42 , which is central to AD pathology [97] as a neurotoxic agent, induced a decrease in the expression of EAAT1 and EAAT2 in cultured astrocytes [98]. Using an elegant approach of in vivo two-photon microscopical de-tection of glutamate with iGluSnFR [99], Hefendehl et al [100] have found that glutamate fluctuates and EAAT2 is downregulated in the vicinity of Amyloid-β plaques. Increasing the glutamate transporter EAAT2 expression by gain-of-function gene targeting [101,102] ameliorated this phenotype [100].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Glial Glutamate Transporter-Mediated Plasticity: System xc-/xCT/SLC7A11 and EAAT1/2 in Brain Diseases

Dahlmanns¹,

Dahlmanns²,

Savaskan³

et al. 2023

Front. Biosci. (Landmark Ed)

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Glial cells play an essential role in the complex function of the nervous system. In particular, astrocytes provide nutritive support for neuronal cells and are involved in regulating synaptic transmission. Oligodendrocytes ensheath axons and support information transfer over long distances. Microglial cells constitute part of the innate immune system in the brain. Glial cells are equipped with the glutamatecystine-exchanger xCT (SLC7A11), the catalytic subunit of system xc − , and the excitatory amino acid transporter 1 (EAAT1, GLAST) and EAAT2 (GLT-1). Thereby, glial cells maintain balanced extracellular glutamate levels that enable synaptic transmission and prevent excitotoxic states. Expression levels of these transporters, however, are not fixed. Instead, expression of glial glutamate transporters are highly regulated in reaction to the external situations. Interestingly, such regulation and homeostasis is lost in diseases such as glioma, (tumor-associated) epilepsy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis or multiple sclerosis. Upregulation of system xc − (xCT or SLC7A11) increases glutamate export from the cell, while a downregulation of EAATs decreases intracellular glutamate import. Occurring simultaneously, these reactions entail excitotoxicity and thus harm neuronal function. The release of glutamate via the antiporter system xc − is accompanied by the import of cystine-an amino acid essential in the antioxidant glutathione. This homeostasis between excitotoxicity and intracellular antioxidant response is plastic and off-balance in central nervous system (CNS) diseases. System xc − is highly expressed on glioma cells and sensitizes them to ferroptotic cell death. Hence, system xc − is a potential target for chemotherapeutic add-on therapy. Recent research reveals a pivotal role of system xc − and EAAT1/2 in tumor-associated and other types of epilepsy. Numerous studies show that in Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, these glutamate transporters are dysregulated-and disease mechanisms could be interposed by targeting system xc − and EAAT1/2. Interestingly, in neuroinflammatory diseases such as multiple sclerosis, there is growing evidence for glutamate transporter involvement. Here, we propose that the current knowledge strongly suggest a benefit from rebalancing glial transporters during treatment.

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Imaging Synaptic Glutamate Release with Two-Photon Microscopy in Organotypic Slice Cultures

Cited by 2 publications

References 9 publications

Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging

Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging

Glial Glutamate Transporter-Mediated Plasticity: System xc-/xCT/SLC7A11 and EAAT1/2 in Brain Diseases

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