RT Journal Article SR Electronic T1 Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.01.972216 DO 10.1101/2020.03.01.972216 A1 Austin R. Graves A1 Richard H. Roth A1 Han L. Tan A1 Qianwen Zhu A1 Alexei M. Bygrave A1 Elena Lopez-Ortega A1 Ingie Hong A1 Alina C. Spiegel A1 Richard C. Johnson A1 Joshua T. Vogelstein A1 Daniel J. Tward A1 Michael I. Miller A1 Richard L. Huganir YR 2021 UL http://biorxiv.org/content/early/2021/09/13/2020.03.01.972216.abstract AB 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 synapses changes during behavior. We used this approach to generate an unprecedentedly detailed spatiotemporal map of synaptic plasticity underlying 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.Competing Interest StatementThe authors have declared no competing interest.