Nagelhus, E. A. | bioRxiv Science

bioRxiv2020

Membrane Ca2+ permeability and IP3R2 dependent Ca2+-induced Ca2+ release are essential for astrocytic intracellular Ca2+ elevation upon neuronal stimulation at the mouse hippocampal CA3 - CA1 excitatory synapses

Astrocytes are intricately involved in the activity of neural circuits, however, their basic physiology of interacting with neurons remains controversial. Using dual-indicator two-photon imaging of neurons and astrocytes during stimulations of hippocampal CA3 - CA1 Schaffer collateral (Scc) excitatory synapses, we report that under physiological conditions, the increased glutamate released from the higher frequency stimulation of neurons can accelerate local astrocytic Ca2+ levels. As consequences of extracellular glutamate clearance and maintaining of astrocytic intracellular Na+ homeostasis, the increase of astrocytic membrane Ca2+ permeability via Na+/Ca2+ exchanger (NCX) reverse mode is the primary reason of eliciting astrocytic intracellular Ca2+ elevation upon neuronal stimulation. This Ca2+-induced Ca2+ release is dependent on inositol triphosphate receptor type 2 (IP3R2). In addition, ATP released from Scc excitatory synapses can contribute to this molecular mechanism of Ca2+-induced Ca2+ release in astrocytes.

neuroscience↗

bioRxiv2019

Ca2+ signaling in astrocytes is sleep-wake state specific and modulates sleep

Astrocytic Ca2+ signaling has been intensively studied in health and disease but remains uncharacterized in sleep. Here, we employed a novel activity-based algorithm to assess astrocytic Ca2+ signals in the barrel cortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We discovered that Ca2+ signaling in astrocytes exhibits distinct features across the sleep-wake cycle and is reduced in sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow-wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Genetic ablation of a key astrocytic Ca2+ signaling pathway resulted in fragmentation of slow-wave sleep, yet increased the frequency of sleep spindles. Our findings suggest a role for astrocytic Ca2+ signaling in modulating sleep.

neuroscience↗