Metamorphosis of memory circuits in Drosophila reveals a strategy for evolving a larval brain

Abstract

Mushroom bodies (MB) of adult Drosophila have a core of thousands of Kenyon neurons; axons of the early-born g class form a medial lobe and those from later-born α'β' and αβ classes form both medial and vertical lobes. The larva, however, hatches with only γ neurons and forms a vertical lobe 'facsimile' using larval-specific axon branches from its γ neurons. MB input (MBINs) and output (MBONs) neurons divide the Kenyon neuron lobes into discrete computational compartments. The larva has 10 such compartments while the adult has 16. We determined the fates of 28 of the 32 MBONs and MBINs that define the 10 larval compartments. Seven compartments are subsequently incorporated into the adult MB; four of their MBINs die, while 12 MBINs/MBONs remodel to function in adult compartments. The remaining three compartments are larval specific. At metamorphosis their MBIN/MBONs trans-differentiate, leaving the MB for other adult brain circuits. The adult vertical lobes are made de novo using MBONs/MBINs recruited from pools of adult-specific neurons. The combination of cell death, compartment shifting, trans-differentiation, and recruitment of new neurons result in no larval MBIN-MBON connections being maintained through metamorphosis. At this simple level, then, we find no anatomical substrate for a memory trace persisting from larva to adult. The adult phenotype of the trans-differentiating neurons represents their evolutionarily ancestral phenotype while their larval phenotype is a derived adaptation for the larval stage. These cells arise primarily within lineages that also produce permanent MBINs and MBONs, suggesting that larval specifying factors may allow information related to birth-order or sibling identity to be interpreted in a modified manner in the larva to allow these neurons to acquire larval phenotypic modifications. The loss of such factors at metamorphosis then allows these neurons to revert to their ancestral functions in the adult.