Quantitative proteomics reveals olfactory input-dependent alterations in the mouse olfactory bulb proteome

Abstract

Olfactory sensory information is processed and integrated by circuits within the olfactory bulb (OB) before being sent to the olfactory cortex. In the mammalian OB, neural activity driven by external stimuli can lead to experience-dependent changes in structures and functions. In this study, quantitative proteomics techniques were employed to study proteome-wide changes in the OB under four levels of neural activity (from low to high): devoid of peripheral input (using a transgenic model), wild-type control, and short-term and long-term odor exposures. Our results revealed that proteins related to various processes were altered in the OBs of odor-deprived and odor-stimulated mice compared to the wild-type controls. These changes induced by odor stimulation were quite different from those induced by a deficit in peripheral olfactory inputs. Detailed analysis demonstrated that metabolic process and synaptic transmission were the most commonly altered pathways and that the effects of peripheral deprivation were more profound. Our comparative proteomics analysis indicated that olfactory deprivation and odor exposure lead to different alterations in the OB proteome, which provides new clues about the mechanisms underlying the olfactory deprivation- or odor stimulation-induced plasticity of OB function and organization.

Biological significance: By combining quantitative proteomics, bioinformatics and WB/IHC analysis, this study reports the results of the first comparative study on proteome-wide changes in the olfactory bulb under different levels of olfactory input. Odor deprivation and stimulation induced proteomic changes clearly demonstrate significant metabolic shifts and alterations on synaptic transmission. This quantitative system biology study leads to a new level of understanding in the development of olfactory bulb plasticity induced by odor deprivation or stimulation, and provides many new clues for the olfactory bulb related functional studies.

Keywords: Metabolic process; Odor deprivation; Odor exposure; Olfactory bulb; Quantitative proteomics; Synaptic transmission.