Loss of IP3 Receptor-Dependent Ca2+ Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity

Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 06/2008; 28(19):4967-73. DOI: 10.1523/JNEUROSCI.5572-07.2008
Source: PubMed


Astrocytes in the hippocampus release calcium (Ca(2+)) from intracellular stores intrinsically and in response to activation of G(q)-linked G-protein-coupled receptors (GPCRs) through the binding of inositol 1,4,5-trisphosphate (IP(3)) to its receptor (IP(3)R). Astrocyte Ca(2+) has been deemed necessary and sufficient to trigger the release of gliotransmitters, such as ATP and glutamate, from astrocytes to modulate neuronal activity. Several lines of evidence suggest that IP(3)R type 2 (IP(3)R2) is the primary IP(3)R expressed by astrocytes. To determine whether IP(3)R2 is the primary functional IP(3)R responsible for astrocytic Ca(2+) increases, we conducted experiments using an IP(3)R2 knock-out mouse model (IP(3)R2 KO). We show, for the first time, that lack of IP(3)R2 blocks both spontaneous and G(q)-linked GPCR-mediated increases in astrocyte Ca(2+). Furthermore, neuronal G(q)-linked GPCR Ca(2+) increases remain intact, suggesting that IP(3)R2 does not play a major functional role in neuronal calcium store release or may not be expressed in neurons. Additionally, we show that lack of IP(3)R2 in the hippocampus does not affect baseline excitatory neuronal synaptic activity as measured by spontaneous EPSC recordings from CA1 pyramidal neurons. Whole-cell recordings of the tonic NMDA receptor-mediated current indicates that ambient glutamate levels are also unaffected in the IP(3)R2 KO. These data show that IP(3)R2 is the key functional IP(3)R driving G(q)-linked GPCR-mediated Ca(2+) increases in hippocampal astrocytes and that removal of astrocyte Ca(2+) increases does not significantly affect excitatory neuronal synaptic activity or ambient glutamate levels.

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Available from: Todd A Fiacco
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    • "Astrocytes are in intimate structural relationship with synaptic contacts and are emerging as active players in development [1], function [2], and plasticity of synapses [3]. Astrocytes exhibit a large number of receptors for different neurotransmitters and the majority of these transmitters signal through G protein-coupled receptors (GPCRs) [4] that lead to IP 3 R2 mediated release of Ca 2+ from intracellular stores [5]. The role of astrocytic Ca 2+ signaling in modulating synaptic transmission , plasticity, and behavior is not fully clear. "
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    • "Ca 2+ signaling in astrocytes has been linked to diverse phenomena, including changes in blood vessel diameter (Attwell et al., 2010; Mulligan and MacVicar, 2004) and synaptic plasticity (Di Castro et al., 2011; Min and Nevian, 2012; Jourdain et al., 2007), suggesting that the impact of astrocytes on various aspects of brain physiology is controlled by these metabotropic receptors. Nevertheless, the role of Ca 2+ signaling in astrocytes in vivo remains uncertain, and mice that lack IP3R2 Ca 2+ release channels that are responsible for receptor-evoked Ca 2+ transients are overtly normal (Petravicz et al., 2008). Our lack of understanding about the interaction of astrocytes with neural circuits reflects our limited knowledge about the behavioral contexts in which astrocyte networks are activated. "
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