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

Abstract

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 behavioural response to an odorant 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.

Critical periods shaping the social brain: A perspective from Drosophila

“…A central role in modulating structural and functional plasticity on both pre-(OSN) and postsynaptic (PN) sites within olfactory glomeruli belongs to a set of multiglomerular inhibitory Local Interneurons (LNs, Figure 2A). [12,14,16] Molecular mechanisms responsible for experience-dependent plasticity within OSN-PN-LN system include cAMP signaling in LNs, [14,16,19] trans-synaptic Notch signaling between OSNs and PNs, [20,21] translational regulation in PNs and LNs, [22,23] as well as pathways downstream of GABA and NMDA receptors ( Figure 2A). [13,16,18] Recent studies discussed below have further extended our knowledge about the diversity of local mechanisms that control CP onset and duration.…”

“…[ 13,16,18 ] Recent studies discussed below have further extended our knowledge about the diversity of local mechanisms that control CP onset and duration. [ 18,19 ] These provide new insights into opportunities for in vivo manipulations with these processes, and highlight strong parallels with basic principles of CP regulation in vertebrate models. [ 1,4 ] Given the great experimental tractability and its relatively simple structure, fly olfactory system has an enormous potential to serve an integrative model of a CP focusing on both fundamental molecular determinants and long‐lasting behavioral consequences of experimental extension and reopening of critical windows.…”

“…A particularly intriguing finding by Chodankar and colleagues (2020) suggests that CP plasticity affecting structure and physiology of neighboring brain regions with similar circuit architecture can be regulated by independent local mechanisms that trigger qualitatively different circuit rearrangements (Figure 2B). [ 19 ] Thus, olfactory glomeruli V and DM5 display CP‐restricted postsynaptic plasticity in corresponding PNs that requires OSN activity and likely involves subsequent modulation of inhibitory LNs that implement feedforward inhibition of PNs (Figures 2A and B). [ 19 ] At the same time, VA6 glomerulus that superficially displays no differences in circuit organization, maintains similar structural and functional plasticity, which is surprisingly not restricted by a CP.…”

“…[ 19 ] Thus, olfactory glomeruli V and DM5 display CP‐restricted postsynaptic plasticity in corresponding PNs that requires OSN activity and likely involves subsequent modulation of inhibitory LNs that implement feedforward inhibition of PNs (Figures 2A and B). [ 19 ] At the same time, VA6 glomerulus that superficially displays no differences in circuit organization, maintains similar structural and functional plasticity, which is surprisingly not restricted by a CP. [ 19 ] This finding opposes a general notion that CP timing is regulated by global mechanisms acting across vast areas of the brain.…”

“…[ 19 ] At the same time, VA6 glomerulus that superficially displays no differences in circuit organization, maintains similar structural and functional plasticity, which is surprisingly not restricted by a CP. [ 19 ] This finding opposes a general notion that CP timing is regulated by global mechanisms acting across vast areas of the brain. Instead, it may apply to a small portion of the sensory circuit that encounters a particular stimulus.…”