title: Astrocyte IP3R2-dependent Ca(2+) signaling is not a major modulator of neuronal pathways governing behavior.
abstract: Calcium-dependent release of gliotransmitters by astrocytes is reported to play a critical role in synaptic transmission and be necessary for long-term potentiation (LTP), long-term depression (LTD) and other forms of synaptic modulation that are correlates of learning and memory. Further, physiological processes reported to be dependent on Ca(2+) fluxes in astrocytes include functional hyperemia, sleep, and regulation of breathing. The preponderance of findings indicate that most, if not all, receptor dependent Ca(2+) fluxes within astrocytes are due to release of Ca(2+) through IP3 receptor/channels in the endoplasmic reticulum. Findings from several laboratories indicate that astrocytes only express IP3 receptor type 2 (IP3R2) and that a knockout of IP3R2 obliterates the GPCR-dependent astrocytic Ca(2+) responses. Assuming that astrocytic Ca(2+) fluxes play a critical role in synaptic physiology, it would be predicted that elimination of astrocytic Ca(2+) fluxes would lead to marked changes in behavioral tests. Here, we tested this hypothesis by conducting a broad series of behavioral tests that recruited multiple brain regions, on an IP3R2 conditional knockout mouse model. We present the novel finding that behavioral processes are unaffected by lack of astrocyte IP3R-mediated Ca(2+) signals. IP3R2 cKO animals display no change in anxiety or depressive behaviors, and no alteration to motor and sensory function. Morris water maze testing, a behavioral correlate of learning and memory, was unaffected by lack of astrocyte IP3R2-mediated Ca(2+)-signaling. Therefore, in contrast to the prevailing literature, we find that neither receptor-driven astrocyte Ca(2+) fluxes nor, by extension, gliotransmission is likely to be a major modulating force on the physiological processes underlying behavior.
authors.affiliation: Curriculum in Neurobiology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Petravicz
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Boyt
authors.affiliation: Curriculum in Neurobiology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA ; Department of Pharmacology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
authors.forename: Ken D
authors.initials: KD
authors.lastname: McCarthy
keywords: IP3 receptor; astrocyte; behavior; calcium; gliotransmission