Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways

Schwarz, Yvonne; Zhao, Na; Kirchhoff, Frank; Bruns, Dieter

doi:10.1038/nn.4647

Cited by 56 publications

(71 citation statements)

References 50 publications

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“…Recent demonstrations that parallel gliotransmission pathways can exist within single astrocytes (Schwarz et al, 2017) lend support to the notion that multiple signaling pathways are available to enable flexible interactions with neurons under different conditions.…”

Section: Discussionmentioning

confidence: 89%

Astrocyte subdomains respond independently in vivo

López‐Hidalgo

Kellner

Schummers

2019

Preprint

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Astrocytes contact thousands of synapses throughout the territory covered by its fine bushy processes. Astrocytes respond to neuronal activity with an increase in calcium concentration that is in turn linked to their capacity to modulate neuronal activity. It remains unclear whether astrocytes behave as a single functional unit that integrates all of these inputs, or if multiple functional subdomains reside within an individual astrocyte. We utilized the topographic organization of ferret visual cortex to test whether local neuronal activity can elicit spatially restricted events within an individual astrocyte. We monitored calcium activity throughout the extent of astrocytes in ferret visual cortex while presenting visual stimuli that elicit coordinated neuronal activity spatially restricted to functional columns. We found visually-driven calcium responses throughout the entire astrocyte that was largely independent in individual subdomains, often responding to different visual stimulus orientations. A model of the spatial interaction of astrocytes and neuronal orientation maps recapitulated these measurements, consistent with the hypothesis that astrocyte subdomains integrate local neuronal activity. Together, these results suggest that astrocyte responses to neural circuit activity are dominated by functional subdomains that respond locally and independently to neuronal activity.

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Section: Discussionmentioning

confidence: 89%

Astrocyte subdomains respond independently in vivo

López‐Hidalgo

Kellner

Schummers

2019

Preprint

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“…We found that CNO treatment in DVC::GFAP hM3Dq mice decreased food intake and induced c‐FOS expression in neighboring neurons; however, the underlying molecular mechanisms by which this occurs remain to be resolved. Astrocytes can modulate the activity of neurons by mechanisms including altered glutamate transport and also via release of neuroactive molecules (e.g., glutamate, ATP, d ‐serine) (Araque et al, ; Gourine et al, ; Matott, Kline, & Hasser, ; Panatier et al, ; Papouin, Dunphy, Tolman, Dineley, & Haydon, ; Schwarz, Zhao, Kirchhoff, & Bruns, ). Critically, glutamatergic signaling is the principal mechanism for communication between the vagus and second‐order NTS neurons (Doyle & Andresen, ) and NTS astrocytes directly sense vagal glutamate release via Ca 2+ ‐permeable AMPA receptors expressed on the cell membrane (McDougal et al, ).…”

Section: Discussionmentioning

confidence: 99%

Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

Macdonald

Holmes

Beall

et al. 2019

Glia

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A role for glial cells in brain circuits controlling feeding has begun to be identified with hypothalamic astrocyte signaling implicated in regulating energy homeostasis. The nucleus of the solitary tract (NTS), within the brainstem dorsal vagal complex (DVC), integrates vagal afferent information from the viscera and plays a role in regulating food intake. We hypothesized that astrocytes in this nucleus respond to, and influence, food intake. Mice fed high‐fat chow for 12 hr during the dark phase showed NTS astrocyte activation, reflected in an increase in the number (65%) and morphological complexity of glial‐fibrillary acidic protein (GFAP)‐immunoreactive cells adjacent to the area postrema (AP), compared to control chow fed mice. To measure the impact of astrocyte activation on food intake, we delivered designer receptors exclusively activated by designer drugs (DREADDs) to DVC astrocytes (encompassing NTS, AP, and dorsal motor nucleus of the vagus) using an adeno‐associated viral (AAV) vector (AAV‐GFAP‐hM3Dq_mCherry). Chemogenetic activation with clozapine‐N‐oxide (0.3 mg/kg) produced in greater morphological complexity in astrocytes and reduced dark‐phase feeding by 84% at 4 hr postinjection compared with vehicle treatment. hM3Dq‐activation of DVC astrocytes also reduced refeeding after an overnight fast (71% lower, 4 hr postinjection) when compared to AAV‐GFAP‐mCherry expressing control mice. DREADD‐mediated astrocyte activation did not impact locomotion. hM3Dq activation of DVC astrocytes induced c‐FOS in neighboring neuronal feeding circuits (including in the parabrachial nucleus). This indicates that NTS astrocytes respond to acute nutritional excess, are involved in the integration of peripheral satiety signals, and can reduce food intake when activated.

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“…The presence of intracellular vesicles containing glutamate, VGLUTs 1 and 2 as well as specific vesicular proteins (v-SNAREs), were described in astrocytes by several research teams (Bezzi et al, 2004;Montana et al, 2004;Ni and Parpura, 2009;Bergersen et al, 2012). Recently, using single and double v-SNARE knockout mice, Schwarz et al (2017) have proven that astrocytes express synaptobrevin II and cellubrevin on distinct vesicle populations and mediate glutamate and neuropeptide Y release through distinct, previously unrecognized, secretion pathways which may be essential in neuron-astrocyte communication. Different experimental strategies that demonstrate a functional role of vesicular release from astrocytes were summarized by Bohmbach et al (2018).…”

Section: Astrocytes Add Significantly To Glutamate Excitotoxicitymentioning

confidence: 99%

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

Kirdajová

Kriška

Tureckova

et al. 2020

Front. Cell. Neurosci.

246

150

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A plethora of neurological disorders shares a final common deadly pathway known as excitotoxicity. Among these disorders, ischemic injury is a prominent cause of death and disability worldwide. Brain ischemia stems from cardiac arrest or stroke, both responsible for insufficient blood supply to the brain parenchyma. Glucose and oxygen deficiency disrupts oxidative phosphorylation, which results in energy depletion and ionic imbalance, followed by cell membrane depolarization, calcium (Ca 2+ ) overload, and extracellular accumulation of excitatory amino acid glutamate. If tight physiological regulation fails to clear the surplus of this neurotransmitter, subsequent prolonged activation of glutamate receptors forms a vicious circle between elevated concentrations of intracellular Ca 2+ ions and aberrant glutamate release, aggravating the effect of this ischemic pathway. The activation of downstream Ca 2+ -dependent enzymes has a catastrophic impact on nervous tissue leading to cell death, accompanied by the formation of free radicals, edema, and inflammation. After decades of "neuron-centric" approaches, recent research has also finally shed some light on the role of glial cells in neurological diseases. It is becoming more and more evident that neurons and glia depend on each other. Neuronal cells, astrocytes, microglia, NG2 glia, and oligodendrocytes all have their roles in what is known as glutamate excitotoxicity. However, who is the main contributor to the ischemic pathway, and who is the unsuspecting victim? In this review article, we summarize the so-far-revealed roles of cells in the central nervous system, with particular attention to glial cells in ischemiainduced glutamate excitotoxicity, its origins, and consequences.

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Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways

Cited by 56 publications

References 50 publications

Astrocyte subdomains respond independently in vivo

Astrocyte subdomains respond independently in vivo

Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

Ischemia-Triggered Glutamate Excitotoxicity From the Perspective of Glial Cells

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