Astrocyte Calcium Signaling: From Observations to Functions and the Challenges Therein

Khakh, Baljit S.; McCarthy, Ken D.

doi:10.1101/cshperspect.a020404

Cited by 206 publications

(173 citation statements)

References 91 publications

(161 reference statements)

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…At present we do not know the nature of the protective signal that spares active synapses from the inhibitory tone. The apparent protection from inhibition could at least in part result from a local positive feedback regulation by the active synapse (20) and likely involving astrocyte Ca 2+ signaling that shows a highly complex spatial and temporal dynamics (15,64,69). Future studies warrant a careful examination of the various synaptically evoked signals to tease apart those crucial for controlling the presynaptic strength decorrelation.…”

Section: Discussionmentioning

confidence: 98%

Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Letellier

Park

Chater

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

117

View full text Add to dashboard Cite

Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the mechanism of heterosynaptic interactions and the heterogeneity of synaptic strengths of pyramidal cell inputs. Heterosynaptic presynaptic plasticity that counterbalances input strengths requires N-methyl-D-aspartate receptors (NMDARs) and astrocytes. Importantly, this mechanism is shared with the mechanism for maintaining highly heterogeneous basal presynaptic strengths, which requires astrocyte Ca 2+ signaling involving NMDAR activation, astrocyte membrane depolarization, and L-type Ca 2+ channels. Intracellular infusion of NMDARs or Ca 2+-channel blockers into astrocytes, conditionally ablating the GluN1 NMDAR subunit, or optogenetically hyperpolarizing astrocytes with archaerhodopsin promotes homogenization of convergent presynaptic inputs. Our findings support the presence of an astrocytedependent cellular mechanism that enhances the heterogeneity of presynaptic strengths of convergent connections, which may help boost the computational power of dendrites.synapse heterogeneity | synaptic strength | astrocyte | hippocampal neuron | heterosynaptic plasticity A n enduring challenge in neurobiology is to understand how neurons set the strengths of their numerous synapses to efficiently process and store different information while maintaining network homeostasis. Electrophysiology and imaging approaches have revealed that synapses display a high degree of functional heterogeneity, even for those sharing the same axon or dendrite (1-3). The observation that synaptic strengths are heterogeneous, in turn, suggests that synapses can operate independently from one another. Accordingly, many studies have demonstrated the input-specificity of Hebbian and also of homeostatic forms of synaptic plasticity, where synaptic changes are restricted to inputs whose activity is altered (4-6). Nevertheless, such a synapse-autonomous behavior could potentially compromise the global network homeostasis by biasing the overall activity toward excitation or depression, and to overcome this issue, it has been proposed that distinct inputs cooperate by coordinating their relative strengths through heterosynaptic interactions (7-9). In support of the idea that synapses behave as interdependent rather than isolated functional units, the restriction of synaptic strength changes to active inputs has been demonstrated to break down at times, with the induction of synaptic plasticity in the stimulated input accompanying either synaptic depression or potentiation of the nonstimulated inputs (10-13). In a highly studied plasticity paradigm of long-term potentiation (LTP) at hippocampal Schaffer collateral-CA1 synapses, tetanic stimulation that induces LTP is often accompanied by presynaptic long-term depression (LTD) of nonstimulated Schaffer collat...

show abstract

Section: Discussionmentioning

confidence: 98%

Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Letellier

Park

Chater

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

117

View full text Add to dashboard Cite

show abstract

“…These include roles for astrocytes in ion homeostasis, neurotransmitter clearance, synapse formation/removal, synaptic modulation and contributions to neurovascular coupling, all of which are reviewed elsewhere [2-4]. From these perspectives, attention has focussed on astrocyte intracellular Ca 2+ signals as a basis to measure, interrogate and ultimately understand their roles within neural circuits [2, 5]. The strong focus on Ca 2+ is based on the knowledge that Ca 2+ is a widely used and important second messenger and on the realisation that astrocytes, unlike neurons, are electrically not excitable [6].…”

Section: Introductionmentioning

confidence: 99%

“…The possibility that astrocytes may contribute to neural circuit function was first proposed almost 25 years ago [7, 8], soon after astrocyte Ca 2+ signals were discovered [5]. Since then astrocyte Ca 2+ signals have been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

“…Organic Ca 2+ indicator dyes, delivered to astrocytes by bulk loading or by intracellular dialysis using patch pipettes, have proven useful to study astrocytes [5]. Fundamental insights have emerged from their use [9-13].…”

Section: Introductionmentioning

confidence: 99%

“…GECIs reveal Ca 2+ signals from entire astrocytes [28]. Thus, GECIs overcome some of the limitations [5, 19] of organic Ca 2+ indicators to study astrocytes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Probing the Complexities of Astrocyte Calcium Signaling

Shigetomi

Patel

Khakh

2016

Trends in Cell Biology

Self Cite

235

197

View full text Add to dashboard Cite

Astrocytes are abundant glial cells that tile the entire central nervous system and mediate well established functions for neurons, blood vessels and other glia. These ubiquitous cells display intracellular Ca2+ signals, which have been intensely studied for 25 years. Recently, the use of improved methods has unearthed the panoply of astrocyte Ca2+ signals and a variable landscape of basal Ca2+ levels. In vivo studies have started to reveal the settings under which astrocytes display behaviorally relevant Ca2+ signaling. Studies in mice have emphasized how astrocyte Ca2+ signaling is altered in distinct neurodegenerative diseases. Progress in the last few years, fueled by methodological advances, has thus reignited interest in astrocyte Ca2+ signaling for brain function and dysfunction.

show abstract

Membrane Associated RNA‐Containing Vesicles Regulate Cortical Astrocytic Microdomain Calcium Transients in Awake Ischemic Stroke Mice

Zhou,

Bai,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Astrocytic processes minutely regulate neuronal activity via tripartite synaptic structures. The precision‐tuning of the function of astrocytic processes is garnering increasing attention because of its significance in promoting brain repair following ischemic stroke. Microdomain calcium (Ca2+) transients in astrocytic processes are pivotal for the functional regulation of these processes. However, the understanding of the alterations and regulatory mechanism of microdomain Ca2+ transients during stroke remains limited. In the present study, a fast high‐resolution, miniaturized two‐photon microscopy is used to show that the levels of astrocytic microdomain Ca2+ transients are significantly reduced in the peri‐infarct area of awake ischemic stroke mice. This finding correlated with the behavioral deficits shown by these mice under freely‐moving conditions. Mitochondrial Ca2+ activity is an important factor driving the microdomain Ca2+ transients. DEAD Box 1 (DDX1) bound to circSCMH1 (a circular RNA involved in vascular post‐stroke repair) facilitates the formation of membrane‐associated RNA‐containing vesicles (MARVs) and enhances the activity of astrocytic microdomain Ca2+ transients, thereby promoting behavioral recovery. These results show that targeting astrocytic microdomain Ca2+ transients is a potential therapeutic approach in stroke intervention.

show abstract

Astrocyte Calcium Signaling: From Observations to Functions and the Challenges Therein

Cited by 206 publications

References 91 publications

Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks

Probing the Complexities of Astrocyte Calcium Signaling

Membrane Associated RNA‐Containing Vesicles Regulate Cortical Astrocytic Microdomain Calcium Transients in Awake Ischemic Stroke Mice

Contact Info

Product

Resources

About