SUMMARY In the mammalian brain, the anatomical structure of neural circuits changes little during adulthood. As a result, adult learning and memory are thought to result from specific changes in synaptic strength. A possible exception is the olfactory bulb (OB), where activity guides interneuron turnover throughout adulthood. These adult-born granule cell (GC) interneurons form new GABAergic synapses that have little synaptic strength plasticity. In the face of persistent neuronal and synaptic turnover, how does the OB balance flexibility, as is required for adapting to changing sensory environments, with perceptual stability? Here we show that high dendritic spine turnover is a universal feature of GCs, regardless of their developmental origin and age. We find matching dynamics among postsynaptic sites on the principal neurons receiving the new synaptic inputs. We further demonstrate in silico that this coordinated structural plasticity is consistent with stable, yet flexible, decorrelated sensory representations. Together, our study reveals that persistent, coordinated synaptic structural plasticity between interneurons and principal neurons is a major mode of functional plasticity in the OB.

Much of the computational power of the mammalian brain arises from its extensive top-down projections. To enable neuron-specific information processing these projections have to be precisely targeted. How such a specific connectivity emerges and what functions it supports is still poorly understood. We addressed these questions in silico in the context of the profound structural plasticity of the olfactory system. At the core of this plasticity are the granule cells of the olfactory bulb, which integrate bottom-up sensory inputs and top-down inputs delivered by vast top-down projections from cortical and other brain areas. We developed a biophysically supported computational model for the rewiring of the top-down projections and the intra-bulbar network via adult neurogenesis. The model captures various previous physiological and behavioral observations and makes specific predictions for the cortico-bulbar network connectivity that is learned by odor exposure and environmental contexts. Specifically, it predicts that—after learning—the granule-cell receptive fields with respect to sensory and with respect to cortical inputs are highly correlated. This enables cortical cells that respond to a learned odor to enact disynaptic inhibitory control specifically of bulbar principal cells that respond to that odor. For this the reciprocal nature of the granule cell synapses with the principal cells is essential. Functionally, the model predicts context-enhanced stimulus discrimination in cluttered environments (‘olfactory cocktail parties’) and the ability of the system to adapt to its tasks by rapidly switching between different odor-processing modes. These predictions are experimentally testable. At the same time they provide guidance for future experiments aimed at unraveling the cortico-bulbar connectivity.

Much of the computational power of the mammalian brain arises from its extensive top-down projections. To enable neuron-specific information processing these projections have to be precisely targeted. How such a specific connectivity emerges and what functions it supports is still poorly understood. We addressed these questions in silico in the context of the profound structural plasticity of the olfactory system. At the core of this plasticity are the granule cells of the olfactory bulb, which integrate bottom-up sensory inputs and top-down inputs delivered by vast top-down projections from cortical and other brain areas. We developed a biophysically supported computational model for the rewiring of the top-down projections and the intra-bulbar network via adult neurogenesis. The model captures various previous physiological and behavioral observations and makes specific predictions for the cortico-bulbar network connectivity that is learned by odor exposure and environmental contexts. Specifically, it predicts that after learning the granule-cell receptive fields with respect to sensory and with respect to cortical inputs are highly correlated. This enables cortical cells that respond to a learned odor to enact disynaptic inhibitory control specifically of bulbar principal cells that respond to that odor. Functionally, the model predicts context-enhanced stimulus discrimination in cluttered environments ('olfactory cocktail parties') and the ability of the system to adapt to its tasks by rapidly switching between different odor-processing modes. These predictions are experimentally testable. At the same time they provide guidance for future experiments aimed at unraveling the cortico-bulbar connectivity. Author summaryIn mammalian sensory processing, extensive top-down feedback from higher brain areas reshapes the feedforward, bottom-up information processing. The structure of the top-down connectivity, the mechanisms leading to its specificity, and the functions it supports are still poorly understood. Using computational modeling, we investigated these issues in the olfactory system. There, the granule cells of the olfactory bulb, which is the first brain area to receive sensory input from the nose, are the key players of extensive structural changes to the network through the addition and also the removal of granule cells as well as through the formation and removal of their connections. This structural plasticity allows the system to learn and to adapt its sensory processing to its PLOS 1/21 odor environment. Crucially, the granule cells combine bottom-up sensory input from the nose with top-down input from higher brain areas, including cortex. Our biophysically supported computational model predicts that, after learning, the granule cells enable cortical neurons that respond to a learned odor to gain inhibitory control of principal neurons of the olfactory bulb, specifically of those that respond to the learned odor. Functionally, this allows top-down input to enhance odor discrimination in cluttered envir...