Astrocytes exist throughout the CNS and are proposed to affect neural circuits and behaviour through intracellular Ca2+ signaling. Studying the function(s) of astrocyte Ca2+ signaling has proven difficult because of the paucity of tools to achieve selective attenuation. Based on recent studies, we generated and used male and female knock-in mice for Cre-dependent expression of mCherry-tagged hPMCA2w/b in order to attenuate astrocyte Ca2+ signaling in genetically defined cells in vivo (CalExflox mice for Calcium Extrusion). We characterized CalExflox mice following local AAV-Cre microinjections into the striatum and found reduced astrocyte Ca2+ signaling (∼90%) accompanied with repetitive self-grooming behaviour. We also crossed CalExflox mice to astrocyte specific Aldh1l1 -Cre/ERT2 mice in order to achieve inducible global CNS-wide Ca2+ signaling attenuation. Within six days of induction in the bigenic mice, we observed significantly altered ambulation in the open field, disrupted motor coordination and ga...