Figure 9. Toll receptors topographically modulate experience-dependent structural brain plasticity.

(A) Experience – that is stimulation through vision - alters the size of multiple brain domains, including optic lobes (for vision), central brain (integration, equivalent to mammalian cortex) and Kenyon cells (learning and memory). (B) Topographic distribution of Tolls in the brain reveals: (1) a map of Toll expression profiles coincident with anatomical brain domains; (2) profiles specific to each Toll; (3) complementary patterns in neuropiles of the visual system and central complex (fan shaped body, ellipsoid body); (4) overlapping distributions in optic lobes, protocerebral bridge, Kenyon cells and mushroom bodies. Each brain module and neuropile expresses a different Toll or combination of Tolls, which can potentially regulate each region differentially in development and in the adult brain. (C) Activity-dependent adult neurogenesis via Toll receptors. Neuronal activation at the adult critical period increased cell number through a Toll-2-dependent mechanism. Toll receptors can signal via MyD88 or Wek in the adult brain. Via MyD88, they maintain adult progenitor cells quiescent, and thus repress cell proliferation. Via Wek, they promote progenitor cell cycling and proliferation, which also requires Yki. How Wek relates to Yki has not been solved (question marks indicate conceivable alternatives). Conditional over-expression of wek restricted to the adult critical period increases brain size. Thus, Tolls can promote cell proliferation in the adult brain through a novel mechanism involving Wek and Yki, that antagonizes the function of MyD88 in promoting quiescence.