Loss of IP3 receptor-dependent Ca2+ increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity.
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.
Petravicz
Jeremy
J
Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. jeremy_petravicz@med.unc.edu
Fiacco
Todd A
TA
McCarthy
Ken D
KD
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009991:Oscillometry; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D015854:Up-Regulation
D053496:Inositol 1,4,5-Trisphosphate Receptors; D043562:Receptors, G-Protein-Coupled; D018698:Glutamic Acid; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium