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 Drosophila. Here, we asked if Toll receptors are involved. Tolls demarcate a map of brain anatomical domains. Focusing on Toll-2, 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 Tolls synergistically reduced brain size. Conditional over-expression of Toll-2 and wek 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.
Highlights
Structural brain plasticity and neurodegeneration reveal generative and destructive processes operating in the brain
To find out whether Toll receptors are expressed in the brain, we looked for Toll transcripts in embryos and dissected central nervous systems (CNSs) from larvae to adult brains, using reverse-transcription Polymerase Chain Reaction (PCR) (RT-PCR) (Figure 1—figure supplement 1)
Toll-3 transcripts were absent from larval L2 CNSs; Toll-4 and À9 mRNAs were barely detected in all sample types; whereas Toll-1,2, À5,6, À7,8 were expressed in embryos, larval (L2, L3) CNSs, and pupal and adult fly heads (Figure 1—figure supplement 1)
Summary
Structural brain plasticity and neurodegeneration reveal generative and destructive processes operating in the brain. Structural brain plasticity affects the brain topographically, influencing the specific regions involved in experience-dependent processing. These manifestations suggest that brain function is encoded in physical changes to cells. Breeding adult flies in constant darkness decreases, and in constant light increases brain volume (Barth and Heisenberg, 1997; Barth et al, 1997). Breeding adult flies in isolation vs crowded conditions, or in single sex vs mixed groups, causes brain volume changes (Technau, 1984; Heisenberg et al, 1995). The molecular mechanisms underlying structural brain plasticity are unknown, and discovering them is crucial to understand the normal functionality of the brain as well as its pathological responses to disease
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