Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors

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.