Top-down inputs drive neuronal network rewiring and context-enhanced sensory processing in olfaction

Abstract

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.

Context-dependent plasticity of adult-born neurons regulated by cortical feedback

“…It also remains possible that piriform feedback has an additional level of selectivity. For example, it is possible that each piriform feedback axon selectively excites abGCs whose odor tuning matches that of the piriform axon (41). Such a selective wiring scheme would achieve an efficient way to enhance the plasticity of task-relevant abGCs.…”

Structural Spine Plasticity in Olfaction: Memory and Forgetting, Enhanced vs. Reduced Discriminability after Learning

“…Many experiments found that the survival of the abGCs depends on their activity [42,43]. Modeling studies showed that such activity-dependent survival naturally leads to bulbar network structures that are quite similar to those resulting from structural spine plasticity discussed here and similarly enhance odor discrimination [13,14]. Recent experiments have questioned, however, the previously reported extensive cell death of abGCs [44].…”

“…If the top-down connectivity was able to target specific GCs, top-down inputs could control bulbar processing by inhibiting very specific MCs. Computational modeling [14] suggests that the extensive adult neurogenesis of GCs observed in the bulb naturally leads to a network structure that allows just that. That model predicts that non-olfactory contexts that have been associated with a familiar odor allow to suppress that odor, enhancing the detection and discrimination of novel odors.…”

“…In our firing-rate model (1,2) the MC-activity exhibits fluctuations only on the time scale of network restructuring, which is much longer than the odor presentation. Assuming, as in [14], that the MC firing rates M…”

Interneuron activity-structural plasticity association is driven by context-dependent sensory experience

“…A prominent feature of the OB circuit is the extensive top-down projections that predominantly target GCs, allowing higher brain areas to modify OB odor processing. Previous modeling suggests that GC adult neurogenesis naturally leads to a network structure enabling higher brain areas to inhibit specific MCs that allows context-dependent odor-processing in the bulb 45 . Since the GC spine plasticity mimics neurogenesis by sharing the an almost unlimited level of plasticity, albeit local activity/plasticity versus an entirely newly integrated cell, it is expected that mature GC spines contribute by providing specific control of bulbar processing influenced by higher brain areas.…”