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‘Top‐down’ modulation of interneuron survival in the olfactory bulb (Commentary on Komano‐Inoue et al.)

Targeted, apoptotic elimination of neurons is a hallmark of development of the CNS, whereby activity-dependent survival mechanisms refine the connectivity of neuronal networks. In the highly plastic olfactory bulb (OB), persistent turnover of specific interneurons, mainly c-aminobutyric acid (GABA)ergic granule cells, occurs throughout the life of an animal. So, just as Michelangelo described about his own technique for creating masterpieces, ‘Every block of stone has a statue inside it and it is the task of the sculptor to discover it’, the intricate processes of neuronal production and targeted cell death sculpt the formation, maintenance and function of the OB circuits. In this issue of European Journal of Neuroscience, Komano-Inoue et al. (2014) observed that OB granule cells undergo a heightened period of apoptosis within hours after the animal eats a meal (postprandial); they demonstrate that this effect is caused by top-down inputs from the piriform cortex that provide a ‘reorganizing signal’ to the OB. First, these investigators electrically stimulated the piriform inputs to the OB and showed that this caused increased apoptosis of the granule cells. Next, they implanted electrodes into the piriform cortex and monitored the activity during the postprandial period. They discovered enhanced simultaneous sharp wave activity, associated with episodes of slow-wave sleep. Furthermore, by infusing a GABA agonist into the piriform cortex to inhibit the simultaneous sharp waves, the postprandial-induced apoptosis of granule cells in the OB was blocked. Finally, the authors demonstrated that this top-down reorganizing signal is not occluded by sensory deprivation, a condition known to induce granule cell apoptosis, as well. These findings provide strong evidence in support of the hypothesis that piriform cortex firing patterns are responsible for this apoptosis and may represent a mechanism of granule cell circuit refinement during sleep replay. As with any exciting discovery, this study raises numerous questions to be pursued in the future. The next steps to characterize this postprandial effect on apoptosis would be to identify the specific inputs to the OB that are responsible for providing this reorganizing signal. Targeted stimulation or inhibition using optogenetics may offer better spatial and temporal specificity as compared with direct infusion of drugs in the current study. These methods could be combined with Cre-recombinase mouse models to explore the specific neuronal subtypes in the piriform cortex that are responsible for generating the reorganizing signal. Additional key questions to be addressed by future research concern the functional significance of such reorganization and whether the process of cell elimination by the piriform cortex is linked to sleep patterns. The results by Komano-Inoue et al. (2014) motivate future studies aimed at defining the functions of piriform–OB reorganizing signals in learning, memory and behavior.