Syncytial isopotentiality, resulting from a strong electrical coupling, emerges as a physiological mechanism that coordinates individual astrocytes to function as a highly efficient system in brain homeostasis. However, whether syncytial isopotentiality occurs selectively to certain brain regions or is universal to astrocytic networks remains unknown. Here, we have explored the correlation of syncytial isopotentiality with different astrocyte subtypes in various brain regions. Using a nonphysiological K+‐free/Na+electrode solution to depolarize a recorded astrocyte in situ, the existence of syncytial isopotentiality can be revealed: the recorded astrocyte's membrane potential remains at a quasi‐physiological level due to strong electrical coupling with neighboring astrocytes. Syncytial isopotentiality appears in Layer I of the motor, sensory, and visual cortical regions, where astrocytes are organized with comparable cell densities, interastrocytic distances, and the quantity of directly coupled neighbors. Second, though astrocytes vary in their cytoarchitecture in association with neuronal circuits from Layers I–VI, the established syncytial isopotentiality remains comparable among different layers in the visual cortex. Third, neurons and astrocytes are uniquely organized as barrels in Layer IV somatosensory cortex; interestingly, astrocytes both inside and outside of the barrels do electrically communicate with each other and also share syncytial isopotentiality. Fourth, syncytial isopotentiality appears in radial‐shaped Bergmann glia and velate astrocytes in the cerebellar cortex. Fifth, although fibrous astrocytes in white matter exhibit a distinct morphology, their network syncytial isopotentiality is comparable with protoplasmic astrocytes. Altogether, syncytial isopotentiality appears as a system‐wide electrical feature of astrocytic networks in the brain.
Systems neuroscience is still mainly a neuronal field, despite the plethora of evidence supporting the fact that astrocytes modulate local neural circuits, networks, and complex behaviors. In this article, we sought to identify which types of studies are necessary to establish whether astrocytes, beyond their well‐documented homeostatic and metabolic functions, perform computations implementing mathematical algorithms that sub‐serve coding and higher‐brain functions. First, we reviewed Systems‐like studies that include astrocytes in order to identify computational operations that these cells may perform, using Ca2+transients as their encoding language. The analysis suggests that astrocytes may carry out canonical computations in a time scale of subseconds to seconds in sensory processing, neuromodulation, brain state, memory formation, fear, and complex homeostatic reflexes. Next, we propose a list of actions to gain insight into the outstanding question of which variables are encoded by such computations. The application of statistical analyses based on machine learning, such as dimensionality reduction and decoding in the context of complex behaviors, combined with connectomics of astrocyte–neuronal circuits, is, in our view, fundamental undertakings. We also discuss technical and analytical approaches to study neuronal and astrocytic populations simultaneously, and the inclusion of astrocytes in advanced modeling of neural circuits, as well as in theories currently under exploration such as predictive coding and energy‐efficient coding. Clarifying the relationship between astrocytic Ca2+and brain coding may represent a leap forward toward novel approaches in the study of astrocytes in health and disease.
more » « less- NSF-PAR ID:
- 10459189
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Glia
- Volume:
- 68
- Issue:
- 1
- ISSN:
- 0894-1491
- Page Range / eLocation ID:
- p. 5-26
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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