Loss of IP₃Receptor-Dependent Ca²⁺Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity

Abstract

2ϩ . Furthermore, neuronal G q -linked GPCR Ca 2ϩ 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 2ϩ increases in hippocampal astrocytes and that removal of astrocyte Ca 2ϩ increases does not significantly affect excitatory neuronal synaptic activity or ambient glutamate levels.

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…This does not necessarily imply that elegant experimental manipulations with astroglial Ca 2+ within a certain dynamic range by triggering certain cellular cascades should reproduce such effects (Agulhon et al, 2010; Fiacco et al, 2007; Petravicz et al, 2008) (see (Rusakov et al, 2014; Volterra et al, 2014) for discussion). 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).…”

P2Y1R-Initiated, IP3R-Dependent Stimulation of Astrocyte Mitochondrial Metabolism Reduces and Partially Reverses Ischemic Neuronal Damage in Mouse

“…We found that after an RB-induced photothrombosis, leakage of 2MeSADP across the blood-brain barrier elicited Ca 2 þ increases in astrocytes in control wild-type mice ( Figures 5A and 5B), but not in IP 3 R type2 knockout mice ( Figures 5C and 5D), consistent with the observations of Petravicz and coworkers. 21 The average peak amplitude of wild-type astrocytic Ca 2 þ responses within 50 mm of the clotted vessel was 0.76 ± 0.09 (DF/F, n ¼ 3 mice pooled from 51 cells). Direct measurements of the blood vessel diameter, before (32.3 ± 4.2, n ¼ 6) and after (31.8±5.1, n ¼ 7) astrocytic Ca 2 þ revealed no acute changes in the vasculature.…”

“…IP 3 R type2 knockout mice were utilized, since their astrocytes lack spontaneous and G-protein coupled receptor mediated Ca 2 þ increases. 21 IP 3 R type2 knockout or control wild-type mice were prepared for in vivo cortical imaging using an open-skull preparation, which permitted cortical loading of the Ca 2 þ indicator dye Fluo-4 AM. 22 Mice were then treated and imaged as described above, including tail-vein injection of rose Bengal (RB) and 2MeSADP (100 mM).…”

Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation

“…Previous studies have shown that inositol-1,4,5-trisphosphate (IP3)-dependent calcium release from the endoplasmic reticulum (ER) is important for astrocyte calcium signaling (Petravicz et al 2008;Nizar et al 2013;Takata et al 2013;Srinivasan et al 2015). We examined the involvement of this pathway in sensory stimulation-evoked astrocyte responses by expressing GCaMP6s in astrocytes from Ip3r2 -/-mice and wild-type (WT) littermate controls (Li et al 2005) and selecting sub-cellular ROIs in the same manner as previous experiments (manual selection for endfeet and somata ROIs and automated detection for processes).…”