Since Cajal’s first drawings of Golgi stained neurons, generations of researchers have been fascinated by the small protrusions, termed spines, studding many neuronal dendrites. Most excitatory synapses in the mammalian CNS are located on dendritic spines, making spines convenient proxies for excitatory synaptic presence. When in vivo imaging revealed that dendritic spines are dynamic structures, their addition and elimination were interpreted as excitatory synapse gain and loss, respectively. Spine imaging has since become a popular assay for excitatory circuit remodeling. In this review, we re-evaluate the validity of using spine dynamics as a straightforward reflection of circuit rewiring. Recent studies tracking both spines and synaptic markers in vivo reveal that 20% of spines lack PSD-95 and are short-lived. Although they account for most spine dynamics, their remodeling is unlikely to impact long-term network structure. We discuss distinct roles that spine dynamics can play in circuit remodeling depending on synaptic content.

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.

Highlights d Single-cell-omics reveal OLIG2 + glial progenitors as tumorinitiating cells in MB d OLIG2 + cells are quiescent stem-like in full-blown MB but reemerge during relapse d Ablation of mitotic OLIG2 + cells or deletion of Olig2 impedes MB tumor initiation d OLIG2 activates HIPPO-YAP and AURORA-A/MYCN oncogenic networks to promote MB growth

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.

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