Emerging adulthood is marked by a cortical dendritic arborization phase depending on the actin nucleator Cobl.

Abstract

Puberty triggers significant changes. However, besides the pruning of synapses, little is known about more long-range alterations during brain maturation. Actin filament formation - a process ignited by actin nucleators - is crucial for life and also a driving force behind cellular morphology changes. Yet, the physiological importance of especially the more recently discovered, evolutionary younger actin nucleators largely remain elusive. We demonstrate the consequences of deficiency for the actin nucleator Cobl in the mouse brain. We identify remarkably layer- and age-restricted cortical Cobl KO phenotypes in dendritic arborization that first transiently emerge in layer V in rather young adolescent male mice and then manifested in a similar but more pronounced manner in layer II/III during the age of emerging adulthood. Cobl KO phenotypes were observed in the somatosensory cortex, prefrontal cortex and motor cortex. In WT mouse cortices, we discovered an increase in dendritic arbor complexity occurring during emerging adulthood and thereby identified a long-range process for cortical rewiring upon brain maturation. This dendritic arbor expansion is transient and largely erased during mature adulthood. The transient dendritic arbor expansion during emerging adulthood was accompanied by transient length changes of dendritic spines. Molecularly, the process thus seems to relate to alterations in actin dynamics. Importantly, both of these changes were completely absent in Cobl KO mice. Increased risk-taking of Cobl KO mice point towards a lack of maturity. These observations revealed the actin nucleator Cobl as first molecular component crucial for the identified emerging adulthood-related changes of neurons towards brain maturation.Significance statement Puberty triggers significant changes. We discovered a transient increase in dendritic arbor complexity occurring during emerging adulthood. This identified a long-range process for cortical rewiring during the age of emerging adulthood. Also dendritic spines were transiently rearranged. Both processes turned out to be dependent on the actin nucleator Cobl. We discovered remarkably layer- and age-specific cortical Cobl KO phenotypes in dendritic arborization. These first transiently emerged in layer V in adolescent mice and then manifested in a similar but more pronounced manner in layer II/III during the age of emerging adulthood. This identified the actin nucleator Cobl as the first crucial component for the discovered reorganizations towards brain maturation.