Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Kavli Neuroscience Discovery Institute, Baltimore, United States
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
Alina C Spiegel
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Kavli Neuroscience Discovery Institute, Baltimore, United States
Richard C Johnson
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
Kavli Neuroscience Discovery Institute, Baltimore, United States; Center for Imaging Science, Johns Hopkins University School of Engineering, Baltimore, United States; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States
Daniel J Tward
Kavli Neuroscience Discovery Institute, Baltimore, United States; Center for Imaging Science, Johns Hopkins University School of Engineering, Baltimore, United States; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States
Michael I Miller
Kavli Neuroscience Discovery Institute, Baltimore, United States; Center for Imaging Science, Johns Hopkins University School of Engineering, Baltimore, United States; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, United States
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Kavli Neuroscience Discovery Institute, Baltimore, United States
Elucidating how synaptic molecules such as AMPA receptors mediate neuronal communication and tracking their dynamic expression during behavior is crucial to understand cognition and disease, but current technological barriers preclude large-scale exploration of molecular dynamics in vivo. We have developed a suite of innovative methodologies that break through these barriers: a new knockin mouse line with fluorescently tagged endogenous AMPA receptors, two-photon imaging of hundreds of thousands of labeled synapses in behaving mice, and computer vision-based automatic synapse detection. Using these tools, we can longitudinally track how the strength of populations of synapses changes during behavior. We used this approach to generate an unprecedentedly detailed spatiotemporal map of synapses undergoing changes in strength following sensory experience. More generally, these tools can be used as an optical probe capable of measuring functional synapse strength across entire brain areas during any behavioral paradigm, describing complex system-wide changes with molecular precision.
