A key feature of the mammalian brain is its capacity to adapt in response to experience, in part by remodeling of synaptic connections between neurons. Excitatory synapse rearrangements have been monitored in vivo by observation of dendritic spine dynamics, but lack of a vital marker for inhibitory synapses has precluded their observation. Here, we simultaneously monitor in vivo inhibitory synapse and dendritic spine dynamics across the entire dendritic arbor of pyramidal neurons in the adult mammalian cortex using large volume high-resolution dual color two-photon microscopy. We find that inhibitory synapses on dendritic shafts and spines differ in their distribution across the arbor and in their remodeling kinetics during normal and altered sensory experience. Further, we find inhibitory synapse and dendritic spine remodeling to be spatially clustered, and that clustering is influenced by sensory input. Our findings provide in vivo evidence for local coordination of inhibitory and excitatory synaptic rearrangements.

Summary Older concepts of a hard-wired adult brain have been overturned in recent years by in vivo imaging studies revealing synaptic remodeling, now thought to mediate rearrangements in microcircuit connectivity. Using three-color labeling and spectrally resolved two-photon microscopy, we monitor in parallel the daily structural dynamics (assembly or removal) of excitatory and inhibitory postsynaptic sites on the same neurons in mouse visual cortex in vivo. We find that dynamic inhibitory synapses often disappear and reappear again in the same location. The starkest contrast between excitatory and inhibitory synapse dynamics is on dually innervated spines, where inhibitory synapses frequently recur while excitatory synapses are stable. Monocular deprivation, a model of sensory input-dependent plasticity, shortens inhibitory synapse lifetimes and lengthens intervals to recurrence, resulting in a new dynamic state with reduced inhibitory synaptic presence. Reversible structural dynamics indicates a fundamentally new role for inhibitory synaptic remodeling – flexible, input-specific modulation of stable excitatory connections.

We became aware from a reader that the data graphed in Figure 2E resembled the data graphed in 2F, although the legend indicated otherwise. We investigated and found that panel 2E was indeed a placeholder that was prepared with the data from 2F. Unfortunately, in one of the revisions, we inserted the placeholder rather than the correct final panel. All of the data and statistics we report in the manuscript text and legend are based on the true figure, so these remain correct as published. We are grateful to the reader who brought this unfortunate mistake to our attention and apologize for any confusion caused to our colleagues in the community. The correct panel E is shown below.

eMAP preserves epitopes by purely physical tissue-hydrogel hybridization in swellable tissue-gel networks.

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