Ultrastructural view of astrocyte-astrocyte and astrocyte-synapse contacts within the hippocampus

Kiyoshi, Conrad M.; Aten, Sydney; Arzola, Emily P.; Patterson, Jeremy A.; Taylor, Anne; Du, Yixing; Guiher, Ally M.; Philip, Merna; Camacho, Elizabeth Gerviacio; Mediratta, Devin; Collins, Kelsey A.; Benson, Emily; Kidd, Grahame J.; Terman, David; Zhou, Min

doi:10.1101/2020.10.28.358200

Cited by 14 publications

(19 citation statements)

References 76 publications

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“…While we did observe clear cases of astrocytic rings with gaps (Figure S3), consistent with a recent report (Kiyoshi et al, 2020), we also came across rings that appeared seamless, lacking a clear sign of a gap. The definitive answer regarding the existence of seamless rings will probably require more refined EM analysis with cryofixed samples and better image contrast.…”

Section: Resultssupporting

confidence: 92%

Super‐resolution shadow imaging reveals local remodeling of astrocytic microstructures and brain extracellular space after osmotic challenge

Arizono

Inavalli

Bancelin

et al. 2021

Glia

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The extracellular space (ECS) plays a central role in brain physiology, shaping the time course and spread of neurochemicals, ions, and nutrients that ensure proper brain homeostasis and neuronal communication. Astrocytes are the most abundant type of glia cell in the brain, whose processes densely infiltrate the brain's parenchyma. As astrocytes are highly sensitive to changes in osmotic pressure, they are capable of exerting a potent physiological influence on the ECS. However, little is known about the spatial distribution and temporal dynamics of the ECS that surrounds astrocytes, owing mostly to a lack of appropriate techniques to visualize the ECS in live brain tissue. Mitigating this technical limitation, we applied the recent SUper‐resolution SHadow Imaging technique (SUSHI) to astrocyte‐labeled organotypic hippocampal brain slices, which allowed us to concurrently image the complex morphology of astrocytes and the ECS with unprecedented spatial resolution in a live experimental setting. Focusing on ring‐like astrocytic microstructures in the spongiform domain, we found them to enclose sizable pools of interstitial fluid and cellular structures like dendritic spines. Upon experimental osmotic challenge, these microstructures remodeled and swelled up at the expense of the pools, effectively increasing the physical interface between astrocytic and cellular structures. Our study reveals novel facets of the dynamic microanatomical relationships between astrocytes, neuropil, and the ECS in living brain tissue, which could be of functional relevance for neuron–glia communication in a variety of (patho)physiological settings, for example, LTP induction, epileptic seizures or acute ischemic stroke, where osmotic disturbances are known to occur.

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Section: Resultssupporting

confidence: 92%

Super‐resolution shadow imaging reveals local remodeling of astrocytic microstructures and brain extracellular space after osmotic challenge

Arizono

Inavalli

Bancelin

et al. 2021

Glia

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“…Individual leaflets are typically contacted by multiple synapses (for a definition of leaflets and branches, see the 'Structural organization and classification of astrocytic processes' section). Astrocytic processes can also form 'loops' that bundle together neuronal compartments such as axons [17]. Astrocytes regulate synaptic transmission and plasticity, extrasynaptic signaling, and ionostasis.…”

Section: Glial Componentsmentioning

confidence: 99%

“…primary processes [16][17][18]. Hence, the term 'perisynaptic astrocytic processes' is not equivalent to the definition of 'peripheral astrocytic processes'.…”

Section: Trends In Neurosciencesmentioning

confidence: 99%

Astrocytic processes: from tripartite synapses to the active milieu

Semyanov

Verkhratsky

2021

Trends in Neurosciences

156

115

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We define a new concept of 'active milieu' that unifies all components of nervous tissue (neuronal and glial compartments, extracellular space, extracellular matrix, and vasculature) into a dynamic information processing system. Within this framework, we focus on the role of astrocytic processes, classified into organellecontaining branches and organelle-free leaflets. We argue that astrocytic branches with emanating leaflets are homologous to dendritic shafts with spines. Within the active milieu, astrocytic processes are engaged in reciprocal interactions with neuronal compartments and communication with other cellular and non-cellular elements of the nervous tissue. The concept of the active milieuAxons of neurons provide the input and output of the central nervous system, whereas the intricate web of neurons, glia, and vasculature underlies information processing and defines the central nervous system function as an organ. The concept of tripartite synapse [1] has been instrumental in rethinking the role of astrocytes in synaptic transmission. Subsequent morphological analyses identified additional components of the synaptic structure. These components include microglial processes and the extracellular matrix (ECM), thus upgrading the tripartite paradigm to tetra-or pentapartite synapse [2,3]. These convolutions reflect a high degree of complexity of the perisynaptic microenvironment, a subject of remarkable morphological plasticity. In particular, interactions of synapses with their microenvironment are influenced by the interposition of individual synapses and nearby compartments of non-neuronal cells and extracellular space (ECS). Here we argue that the expanding knowledge on physiological interactions of cellular and non-cellular components of nervous tissue necessitates advancing the concept of 'tri-(multi)-partite synapse' to a concept we name 'active milieu'. The active milieu is based on the dynamic interposition and interaction among compartments of neurons, astrocytes, oligodendrocytes, microglia, blood vessels, ECS, and ECM (Box 1 and Figure 1). In the framework of this concept, neuronal activity not only propagates from one neuron to another but also signals to other cellular and noncellular elements, which respond to this signal and affect all components of nervous tissue.

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“…These results together indicate that the electrical barrier between astrocytes is nearly absent. Recently, ultrastructural details of astrocyte-astrocyte contacts have been revealed that explain how such a low inter-astrocytic resistance could be biophysically achieved ( Kiyoshi et al, 2020 ).…”

Section: Analysis Of Gap Junctional Couplingmentioning

confidence: 99%

Approaches to Study Gap Junctional Coupling

Stephan

Eitelmann

Zhou

2021

Front. Cell. Neurosci.

Self Cite

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Astrocytes and oligodendrocytes are main players in the brain to ensure ion and neurotransmitter homeostasis, metabolic supply, and fast action potential propagation in axons. These functions are fostered by the formation of large syncytia in which mainly astrocytes and oligodendrocytes are directly coupled. Panglial networks constitute on connexin-based gap junctions in the membranes of neighboring cells that allow the passage of ions, metabolites, and currents. However, these networks are not uniform but exhibit a brain region-dependent heterogeneous connectivity influencing electrical communication and intercellular ion spread. Here, we describe different approaches to analyze gap junctional communication in acute tissue slices that can be implemented easily in most electrophysiology and imaging laboratories. These approaches include paired recordings, determination of syncytial isopotentiality, tracer coupling followed by analysis of network topography, and wide field imaging of ion sensitive dyes. These approaches are capable to reveal cellular heterogeneity causing electrical isolation of functional circuits, reduced ion-transfer between different cell types, and anisotropy of tracer coupling. With a selective or combinatory use of these methods, the results will shed light on cellular properties of glial cells and their contribution to neuronal function.

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Ultrastructural view of astrocyte-astrocyte and astrocyte-synapse contacts within the hippocampus

Cited by 14 publications

References 76 publications

Super‐resolution shadow imaging reveals local remodeling of astrocytic microstructures and brain extracellular space after osmotic challenge

Super‐resolution shadow imaging reveals local remodeling of astrocytic microstructures and brain extracellular space after osmotic challenge

Astrocytic processes: from tripartite synapses to the active milieu

Approaches to Study Gap Junctional Coupling

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