Biology subjects

Wilkov, A. J.

Publications and source records attributed to Wilkov, A. J..

2 recordsLinked to original sources

bioRxiv2025

Selective life-long suppression of an odor processing channel in response to critical period experience

Sensory circuits undergo experience-dependent plasticity during early-life critical periods, attuning the nervous system to levels of key environmental stimuli. During a critical period in the Drosophila olfactory system, we found that exposure to ethyl butyrate (EB) induces glial phagocytosis of odorant receptor Or42a-positive olfactory sensory neuron (OSN) axon terminals which terminate in the VM7 glomerulus (Leier and Foden et al., 2025). Here, we extend these findings by establishing functional significance and circuit selectivity in this critical period paradigm. First, using a combination of two-photon Ca2+ imaging and the genetically-encoded voltage indicator ASAP5, we find that Or42a OSN odor-evoked responses are permanently suppressed in animals with critical period odor exposure. Thus, critical period odor exposure results in long-term changes to odor sensitivity in Or42a OSNs. Second, to establish the selectivity of glial pruning for Or42a axon terminals, we examined projection neurons (PNs) postsynaptic to Or42a OSNs as well as a second population of highly EB-responsive OSNs, called Or43b OSNs. We find that (1) within VM7, glial pruning is selective for Or42a terminals, and (2) while Or43b OSNs appear modestly pruned, they maintain their sensitivity to EB. To elucidate this difference, we turned to the Drosophila connectome. We identify striking differences in the scale of inhibitory connectivity to Or42a and Or43b OSNs, suggesting that Or42a OSNs may play a particularly central role in EB odor processing. This study expands our understanding of this critical period plasticity paradigm by demonstrating life-long suppression of pruned Or42a OSNs and establishing its specificity within and between sensory circuits.

neuroscience↗

bioRxiv2024

Glia control experience-dependent plasticity in an olfactory critical period

Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The Drosophila antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience. We recently found that glia shape antennal lobe development in young adults, leading us to ask if glia also drive experience-dependent plasticity during this period. Here we define a critical period for structural and functional plasticity of OSN-PN synapses in the ethyl butyrate (EB)-sensitive glomerulus VM7. EB exposure for the first two days post-eclosion drives large-scale reductions in glomerular volume, presynapse number, and post-synaptic activity. Crucially, pruning during the critical period has long-term consequences for circuit function since both OSN-PN synapse number and spontaneous activity of PNs remain persistently decreased following early-life odor exposure. The highly conserved engulfment receptor Draper is required for this critical period plasticity as ensheathing glia upregulate Draper, invade the VM7 glomerulus, and phagocytose OSN presynaptic terminals in response to critical-period EB exposure. Loss of Draper fully suppresses the morphological and physiological consequences of critical period odor exposure, arguing that phagocytic glia engulf intact synaptic terminals. These data demonstrate experience-dependent pruning of synapses and argue that Drosophila olfactory circuitry is a powerful model for defining the function of glia in critical period plasticity.

neuroscience↗