A Toll-receptor map underlies structural brain plasticity.

Abstract

Experience alters brain structure, but the underlying mechanism remained unknown. Structural plasticity reveals that brain function is encoded in generative changes to cells that compete with destructive processes driving neurodegeneration. At an adult critical period, experience increases fiber number and brain size in <i>Drosophila</i>. Here, we asked if Toll receptors are involved. Tolls demarcate a map of brain anatomical domains. Focusing on <i>Toll-2,</i> loss of function caused apoptosis, neurite atrophy and impaired behaviour. Toll-2 gain of function and neuronal activity at the critical period increased cell number. Toll-2 induced cycling of adult progenitor cells via a novel pathway, that antagonized MyD88-dependent quiescence, and engaged Weckle and Yorkie downstream. Constant knock-down of multiple <i>Tolls</i> synergistically reduced brain size. Conditional over-expression of <i>Toll-2</i> and <i>wek</i> at the adult critical period increased brain size. Through their topographic distribution, Toll receptors regulate neuronal number and brain size, modulating structural plasticity in the adult brain.