Calcium Signals in Astrocyte Microdomains, a Decade of Great Advances

Abstract

The glial cells astrocytes have long been recognized as important neuron-supporting elements in brain development, homeostasis, and metabolism. After the discovery that the reciprocal communication between astrocytes and neurons is a fundamental mechanism in the modulation of neuronal synaptic communication, over the last two decades astrocytes became a hot topic in neuroscience research. Crucial to their functional interactions with neurons are the cytosolic Ca2+ elevations that mediate gliotransmission. Large attention has been posed to the so-called Ca2+microdomains, dynamic Ca2+ changes spatially restricted to fine astrocytic processes including perisynaptic astrocytic processes (PAPs). With presynaptic terminals and postsynaptic neuronal membranes, PAPs compose the tripartite synapse. The distinct spatial-temporal features and functional roles of astrocyte microdomain Ca2+ activity remain poorly defined. However, thanks to the development of genetically encoded Ca2+ indicators (GECIs), advanced microscopy techniques, and innovative analytical approaches, Ca2+ transients in astrocyte microdomains were recently studied in unprecedented detail. These events have been observed to occur much more frequently (∼50–100-fold) and dynamically than somatic Ca2+ elevations with mechanisms that likely involve both IP3-dependent and -independent pathways. Further progress aimed to clarify the complex, dynamic machinery responsible for astrocytic Ca2+ activity at microdomains is a crucial step in our understanding of the astrocyte role in brain function and may also reveal astrocytes as novel therapeutic targets for different brain diseases. Here, we review the most recent studies that improve our mechanistic understanding of the essential features of astrocyte Ca2+ microdomains.

Side-by-side comparison of the effects of Gq- and Gi-DREADD-mediated astrocyte modulation on intracellular calcium dynamics and synaptic plasticity in the hippocampal CA1

“…enhanced mEPSPs in surrounding neurons [ 61 ]. Noteworthy, peripheral astrocytic processes (PAPs) are critically involved in synaptic plasticity and are known to display spotty Ca 2+ transients in their microdomains [ 27 , 62 , 63 ]. Although no elevations in Ca 2+ transients were observed in our study, assessment of Ca 2+ transients was restricted to the soma and large processes, as Ca 2+ -imaging was performed using two-photon Ca 2+ imaging after bolus loading of a chemical dye (OGB-1 AM), which is known to have limited spatial resolution [ 64 – 66 ].…”

Reactive Astrocytosis in a Mouse Model of Chronic Polyamine Catabolism Activation

“…The presence of functional AMPA receptors in the processes appears to be well consistent with the decrease in Spm content in the processes, as intracellular Spm is well known to inhibit the Ca 2+ -permeable AMPA receptor functioning. Ca 2+ entry through these AMPA receptors appears to be relevant to the topic of Ca 2+ microdomains, of the dynamic Ca 2+ changes spatially restricted to fine perisynaptic astrocytic processes [ 35 , 36 ], and of their changes in reactive astrocytosis.…”

Generation and Characterization of a New FRET-Based Ca2+ Sensor Targeted to the Nucleus

“…In addition, given the rapid equilibration between [Ca 2+ ] in the two compartments, nucleoplasm Ca 2+ signals can be used as a tool to contemporarily and comparatively monitor the dynamics of [Ca 2+ ] in organelles, such as ER or mitochondria, and in the cytosol in the same cell and with the same type of probes. Obviously, although the nuclear Ca 2+ dynamics mirrors global cytosolic Ca 2+ changes, nuclear Ca 2+ probes cannot properly report very localized cytosolic Ca 2+ changes, such as those occurring in synaptic terminals or other cytoplasmic microenvironments [25].…”