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The Journal of Neuroscience, February 1, 2003, 23(3):758

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

Grace E. Stutzmann, Frank M. LaFerla, and Ian Parker

Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697-4550

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 IP₃ in pyramidal neurons of mouse prefrontal cortex. Ca²⁺ responses to photoreleased IP₃ varied 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.

Key words: calcium signaling; coincidence detection; electrophysiology; flash photolysis; modulation; prefrontal cortex

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Copyright © 2003 Society for Neuroscience  0270-6474/03/233758-08$05.00/0

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