Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

Abstract

BackgroundNeuronal activity alters calcium ion (Ca2+) dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling.ResultsAttenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved.ConclusionsOur findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

Purinergic P2Y1 Receptors Control Rapid Expression of Plasma Membrane Processes in Hippocampal Astrocytes

“…Accordingly, in the presence of the PLC inhibitor U73122 we observed a retraction in APs. Our observation is in line with data showing that in transgenic mice APs were reduced when calcium signaling was attenuated by genetic expression of an IP3 adsorbent [51]. However, our data show unexpectedly that intracellular inclusion of BAPTA-AM was instead unable to modify APs sprouting.…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…In addition to the much debated astrocyte‐neuron exchange, Ca 2+ rises in astrocytes could also boost the expression level of glutamate transporters (Devaraju et al, 2013), re‐position mitochondria closer to glutamate transporters (Jackson et al, 2014; Ugbode et al, 2014), and regulate neuro‐metabolic coupling with neurons (Bernardinelli et al, 2004; Porras et al, 2008). Recent findings suggest that such Ca 2+ signals could be required for morphological changes in PAPs (Molotkov et al, 2013; Tanaka et al, 2013). …”

Subcellular location of astrocytic calcium stores favors extrasynaptic neuron–astrocyte communication

“…The anatomic and functional relationship between astrocytic processes and synaptic clefts led to the idea of tripartite synapses, in which astrocytes are an important functional component in addition to presynaptic axonal boutons and postsynaptic spines [10,11]. Notably, the coverage of the synapse by PAPs changes under different physiologic conditions and is regulated by the Ca 2+ dynamics in the astrocytes [12,13].…”