Development of the mammalian main olfactory bulb.

The mammalian main olfactory bulb is a crucial processing centre for the sense of smell. The olfactory bulb forms early during development and is functional from birth. However, the olfactory system continues to mature and change throughout life as a target of constitutive adult neurogenesis. Our Review synthesises current knowledge of prenatal, postnatal and adult olfactory bulb development, focusing on the maturation, morphology, functions and interactions of its diverse constituent glutamatergic and GABAergic cell types. We highlight not only the great advances in the understanding of olfactory bulb development made in recent years, but also the gaps in our present knowledge that most urgently require addressing.

Brief Sensory Deprivation Triggers Cell Type-Specific Structural and Functional Plasticity in Olfactory Bulb Neurons.

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odor processing. We induced experience-dependent plasticity in mice of either sex by blocking one nostril for one day, a minimally invasive manipulation that leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory deprivation produced structural and functional plasticity in one highly specialized bulbar cell type: axon-bearing dopaminergic neurons in the glomerular layer. After 24 h naris occlusion, the axon initial segment (AIS) in bulbar dopaminergic neurons became significantly shorter, a structural modification that was also associated with a decrease in intrinsic excitability. These effects were specific to the AIS-positive dopaminergic subpopulation because no experience-dependent alterations in intrinsic excitability were observed in AIS-negative dopaminergic cells. Moreover, 24 h naris occlusion produced no structural changes at the AIS of bulbar excitatory neurons, mitral/tufted and external tufted cells, nor did it alter their intrinsic excitability. By targeting excitability in one specialized dopaminergic subpopulation, experience-dependent plasticity in early olfactory networks might act to fine-tune sensory processing in the face of continually fluctuating inputs.SIGNIFICANCE STATEMENT Sensory networks need to be plastic so they can adapt to changes in incoming stimuli. To see how cells in mouse olfactory circuits can change in response to sensory challenges, we blocked a nostril for just one day, a naturally relevant manipulation akin to the deprivation that occurs with a mild cold. We found that this brief deprivation induces forms of axonal and intrinsic functional plasticity in one specific olfactory bulb cell subtype: axon-bearing dopaminergic interneurons. In contrast, intrinsic properties of axon-lacking bulbar dopaminergic neurons and neighboring excitatory neurons remained unchanged. Within the same sensory circuits, specific cell types can therefore make distinct plastic changes in response to an ever-changing external landscape.

Myosin II activity is required for structural plasticity at the axon initial segment.

In neurons, axons possess a molecularly defined and highly organised proximal region - the axon initial segment (AIS) - that is a key regulator of both electrical excitability and cellular polarity. Despite existing as a large, dense structure with specialised cytoskeletal architecture, the AIS is surprisingly plastic, with sustained alterations in neuronal activity bringing about significant alterations to its position, length or molecular composition. However, although the upstream activity-dependent signalling pathways that lead to such plasticity have begun to be elucidated, the downstream mechanisms that produce structural changes at the AIS are completely unknown. Here, we use dissociated cultures of rat hippocampus to show that two forms of AIS plasticity in dentate granule cells - long-term relocation, and more rapid shortening - are completely blocked by treatment with blebbistatin, a potent and selective myosin II ATPase inhibitor. These data establish a link between myosin II and AIS function, and suggest that myosin II's primary role at the structure may be to effect activity-dependent morphological alterations.