The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity (NACA) in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that NACA influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathologic models.

Center for In Vivo Microscopy Department of Radiology Duke University Medical Center Durham NC 27710

Center for Research on Cancer in Lyon University of Lyon Lyon 69008 France

Department of Anatomy and Cell Biology University of Western Ontario London Ontario N6A 3K7 Canada

Department of Biomedical Engineering Duke University Medical Center Durham NC 27710

Department of Cell Biology Duke University Medical Center Durham NC 27710

Department of Medicine Duke University Medical Center Durham NC 27710

Department of Neurobiology Duke University Medical Center Durham NC 27710

Department of Pharmacology and Cancer Biology Duke University Medical Center Durham NC 27710

Department of Physics Duke University Durham NC 27710

Department of Physiology and Pharmacology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario N6A 3K7 Canada

Department of Psychiatry and Behavioral Sciences Duke University Medical Center Durham NC 27710

Department of Surgery Duke University Medical Center Durham NC 27710

Institute of Biology Charles University Plzen CZ 32300 Czech Republic

Robarts Research Institute University of Western Ontario London Ontario N6A 3K7 Canada

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