Glomerulus-Selective Regulation of a Critical Period for Interneuron Plasticity in the Drosophila Antennal Lobe

Several features of the adult nervous systems develop in a “critical period” (CP), during which high levels of plasticity allow neural circuits to be tuned for optimal performance. Through an analysis of long-term olfactory habituation (LTH) in female Drosophila, we provide new insight into mechanisms by which CPs are regulated in vivo. LTH manifests as a persistently reduced behavioral response to an odorant encountered for 4 continuous days and occurs together with the growth of specific, odorant-responsive glomeruli in the antennal lobe. We show that the CP for behavioral and structural plasticity induced by ethyl butyrate (EB) or carbon dioxide (CO(2)) closes within 48 h after eclosion. The elaboration of excitatory projection neuron (PN) processes likely contribute to glomerular volume increases, as follows: both occur together and similarly require cAMP signaling in the antennal lobe inhibitory local interneurons. Further, the CP for structural plasticity could be extended beyond 48 h if EB- or CO(2)-responsive olfactory sensory neurons (OSNs) are silenced after eclosion; thus, OSN activity is required for closing the CP. Strikingly, silencing of glomerulus-selective OSNs extends the CP for structural plasticity only in respective target glomeruli. This indicates the existence of a local, short-range mechanism for regulating CP closure. Such a local mechanism for CP regulation can explain why plasticity induced by the odorant geranyl acetate (which is attractive) shows no CP although it involves the same core plasticity mechanisms as CO(2) and EB. Local control of closure mechanisms during the critical period can potentially impart evolutionarily adaptive, odorant-specific features to behavioral plasticity. SIGNIFICANCE STATEMENT The critical period for plasticity represents a stage of life at which animals learn specific tasks or features with particular facility. This work provides fresh evidence that mechanisms for regulating critical periods are broadly conserved across evolution. Thus, a critical period for long-term olfactory habituation in Drosophila, which closes early in adulthood can, like the critical period for ocular dominance plasticity in mammals, be extended by blocking sensory neurons early in life. Further observations show that critical periods for plasticity can be regulated by spatially restricted mechanisms, potentially allowing varied critical periods for plasticity to stimuli of different ethological relevance.