Ca2+Signaling in Mouse Cortical Neurons Studied by Two-Photon Imaging and Photoreleased Inositol Triphosphate

IP3-mediated Ca2+release is a crucial neuronal signaling mechanism that has not been extensively characterized in the mammalian cerebral cortex. We used two-photon, video-rate microscopy to image Ca2+signals evoked by photoreleased IP3in pyramidal neurons of mouse prefrontal cortex. Ca2+responses to photoreleased IP3varied greatly between different neurons; however, within IP3-responsive neurons, the soma invariably showed highest sensitivity, with signals increasing nonlinearly with [IP3]. Responses to paired photorelease displayed inhibition, whereas IP3-evoked Ca2+liberation was potentiated by Ca2+entry during action potentials and vice versa. IP3-mediated Ca2+signals strongly inhibited spike firing through activation of K+membrane conductance. Metabotropic signaling via the phosphoinositide pathway thus serves as a powerful and sustained modulator of excitability in cortical neurons and displays complex reciprocal interactions between electrical and chemical signals.