Serotonin acts through multiple cellular targets during an olfactory critical period.

Serotonin (5-HT) is known to modulate early development during critical periods when experience drives heightened levels of plasticity in neurons. Here, we take advantage of the genetically tractable olfactory system of Drosophila to investigate how 5-HT modulates critical period plasticity in the CO2 sensing circuit of fruit flies. Our study reveals that 5HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit. The olfactory CPP is known to involve local inhibitory networks and consistent with this we found that knocking down 5-HT7 receptors in a subset of GABAergic local interneurons was sufficient to block CPP, as was knocking down GABA receptors expressed by olfactory sensory neurons (OSNs). Additionally, direct modulation of OSNs via 5-HT2B expression in the cognate OSNs sensing CO2 is also essential for CPP. Furthermore, 5-HT1B expression by serotonergic neurons in the olfactory system is also required during the critical period. Our study reveals that 5-HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit.

Olfactory Critical Periods: How Odor Exposure Shapes the Developing Brain in Mice and Flies.

Neural networks have an extensive ability to change in response to environmental stimuli. This flexibility peaks during restricted windows of time early in life called critical periods. The ubiquitous occurrence of this form of plasticity across sensory modalities and phyla speaks to the importance of critical periods for proper neural development and function. Extensive investigation into visual critical periods has advanced our knowledge of the molecular events and key processes that underlie the impact of early-life experience on neuronal plasticity. However, despite the importance of olfaction for the overall survival of an organism, the cellular and molecular basis of olfactory critical periods have not garnered extensive study compared to visual critical periods. Recent work providing a comprehensive mapping of the highly organized olfactory neuropil and its development has in turn attracted a growing interest in how these circuits undergo plasticity during critical periods. Here, we perform a comparative review of olfactory critical periods in fruit flies and mice to provide novel insight into the importance of early odor exposure in shaping neural circuits and highlighting mechanisms found across sensory modalities.