Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice

Institóris, Ádám; Vandal, Milène; Peringod, Govind; Catalano, Christy; Tran, Cam Ha T.; Yu, Xinzhu; Visser, Frank; Breiteneder, Cheryl; Molina, Leonardo A.; Khakh, Baljit S.; Nguyen, Minh Dang; Thompson, Roger; Gordon, Grant R.

doi:10.1038/s41467-022-35383-2

Cited by 24 publications

(32 citation statements)

References 97 publications

(142 reference statements)

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“…In most cases, Ca 2+ microdomains exhibiting fast onset were a subset of all astrocytic responses occurring upon neuronal activation. An important conclusion that we can derive from these and other experimental works [see, for example, ( Institoris et al, 2022 )] is that astrocytes display both fast and delayed responses during functional hyperemia, most likely playing different roles in initiating and maintaining vasodilatation. Many of the studies concluding that astrocyte response is too slow to be involved in vasodilatation onset present astrocyte response as an average time course of all Ca 2+ signals recorded in processes or endfeet, thus diluting fast signals, whereas a more correct approach requires isolating the subset of fast responses to characterize their properties.…”

Section: A Role For Astrocyte Ca 2+mentioning

confidence: 53%

“…For these reasons, raising the bar to an in vivo awake experimental approach avoids this possible source of controversies. NVC can be studied in vivo upon direct stimulation of brain activity by sensory stimulation ( Institoris et al, 2022 ), or upon specific cell type stimulation. Over the past decades, optogenetics has been established as one of the most powerful ways to drive the activation of specific brain cells ( Deisseroth, 2015 ).…”

Section: How To Study Astrocyte Role In Nvcmentioning

confidence: 99%

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Two decades of astrocytes in neurovascular coupling

Lia

Spiezio

Speggiorin

et al. 2023

Front. Netw. Physiol.

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The brain is a highly energy demanding organ, which accounts in humans for the 20% of total energy consumption at resting state although comprising only 2% of the body mass. The necessary delivery of nutrients to brain parenchyma is ensured by the cerebral circulatory system, through the exchange of glucose and oxygen (O2) at the capillary level. Notably, a tight spatial and temporal correlation exists between local increases in neuronal activity and the subsequent changes in regional cerebral blood flow. The recognized concept of neurovascular coupling (NVC), also named functional hyperemia, expresses this close relationship and stands at the basis of the modern functional brain imaging techniques. Different cellular and molecular mechanisms have been proposed to mediate this tight coupling. In this context, astrocytes are ideally positioned to act as relay elements that sense neuronal activity through their perisynaptic processes and release vasodilator agents at their endfeet in contact with brain parenchymal vessels. Two decades after the astrocyte involvement in neurovascular coupling has been proposed, we here review the experimental evidence that contributed to unraveling the molecular and cellular mechanisms underlying cerebral blood flow regulation. While traveling through the different controversies that moved the research in this field, we keep a peculiar focus on those exploring the role of astrocytes in neurovascular coupling and conclude with two sections related to methodological aspects in neurovascular research and to some pathological conditions resulting in altered neurovascular coupling.

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Section: A Role For Astrocyte Ca 2+mentioning

confidence: 53%

Section: How To Study Astrocyte Role In Nvcmentioning

confidence: 99%

Two decades of astrocytes in neurovascular coupling

Lia

Spiezio

Speggiorin

et al. 2023

Front. Netw. Physiol.

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show abstract

“…S3). In addition, it has been recently suggested that astrocytes may play a key role in the amplification of functional hyperemia to sustained stimulation, which could be also be part of future studies within our model 66 . On the other hand, inhibitory neurons may also be www.nature.com/scientificreports/ involved in Functional Hyperemia 29 , for example via the release of nitric oxide (which is a known vasodilator) or even via interaction with astrocytic end-feet as has recently been suggested 13 .…”

Section: Discussionmentioning

confidence: 96%

Modeling the relationship between neuronal activity and the BOLD signal: contributions from astrocyte calcium dynamics

Tesler

Linne

Destexhe

2023

Sci Rep

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Functional magnetic resonance imaging relies on the coupling between neuronal and vascular activity, but the mechanisms behind this coupling are still under discussion. Recent experimental evidence suggests that calcium signaling may play a significant role in neurovascular coupling. However, it is still controversial where this calcium signal is located (in neurons or elsewhere), how it operates and how relevant is its role. In this paper we introduce a biologically plausible model of the neurovascular coupling and we show that calcium signaling in astrocytes can explain main aspects of the dynamics of the coupling. We find that calcium signaling can explain so-far unrelated features such as the linear and non-linear regimes, the negative vascular response (undershoot) and the emergence of a (calcium-driven) Hemodynamic Response Function. These features are reproduced here for the first time by a single model of the detailed neuronal-astrocyte-vascular pathway. Furthermore, we analyze how information is coded and transmitted from the neuronal to the vascular system and we predict that frequency modulation of astrocytic calcium dynamics plays a key role in this process. Finally, our work provides a framework to link neuronal activity to the BOLD signal, and vice-versa, where neuronal activity can be inferred from the BOLD signal. This opens new ways to link known alterations of astrocytic calcium signaling in neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s diseases) with detectable changes in the neurovascular coupling.

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“…For example, is mural cell coverage and contractility intact in blood vessels after CIH and reoxygenation? Have astrocytes populated the perivascular niche and are their endfeet properly aligned with the vessel wall and able to support their roles in BBB function [[106]] and neurovascular coupling [[107], [108]]? Are the various zones within the cerebrovasculature (arterioles, capillaries, venules, and intervening transitional segments) properly formed and correct in their length proportions?…”

Section: Consequences Of Cih On Cerebrovascular Structure and Functionmentioning

confidence: 99%

Does Perinatal Intermittent Hypoxia Affect Cerebrovascular Network Development?

Coelho-Santos¹,

Cruz²,

Shih³

2023

Dev Neurosci

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Perinatal hypoxia is an inadequate delivery of oxygen to the fetus in the period immediately before, during, or after the birth process. The most frequent form of hypoxia occurring in human development is chronic intermittent hypoxia (CIH) due to sleep-disordered breathing (apnea) or bradycardia events. CIH incidence is particularly high with premature infants. During CIH, repetitive cycles of hypoxia and reoxygenation initiate oxidative stress and inflammatory cascades in the brain. A dense microvascular network of arterioles, capillaries, and venules is required to support the constant metabolic demands of the adult brain. The development and refinement of this microvasculature is orchestrated throughout gestation and in the initial weeks after birth, at a critical juncture when CIH can occur. There is little knowledge on how CIH affects the development of the cerebrovasculature. However, since CIH (and its treatments) can cause profound abnormalities in tissue oxygen content and neural activity, there is reason to believe that it can induce lasting abnormalities in vascular structure and function at the microvascular level contributing to neurodevelopmental disorders. This mini-review discusses the hypothesis that CIH induces a positive feedback loop to perpetuate metabolic insufficiency through derailment of normal cerebrovascular development, leading to long-term deficiencies in cerebrovascular function.

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Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice

Cited by 24 publications

References 97 publications

Two decades of astrocytes in neurovascular coupling

Two decades of astrocytes in neurovascular coupling

Modeling the relationship between neuronal activity and the BOLD signal: contributions from astrocyte calcium dynamics

Does Perinatal Intermittent Hypoxia Affect Cerebrovascular Network Development?

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