Functional Activity And Connectivity In Olfactory Bulbs Under Pathological And Physiological States

Olfaction plays an important role in animal and human’s life. It is crucial for animals to find food, mark territory, and recognize conspecies and predators. For humans, odors provide information about food and environment. Olfaction influences feeding behavior and social interactions, and in turn, nutrition or attention status affects olfaction. The olfactory bulb (OB) is the first information processing center of the olfactory system, it is important in the odor information coding and transmission to the central olfactory regions. In the meanwhile, it receives lots of centrifugal projections. The centrifugal modulation provides the possibility that the functional activity and the connectivity between the bilateral OBs could be modulated by different brain states. The main purpose of the present thesis is to reveal the characteristics of the OB activity and how OB processes odor information when the animals are under pathological (such as Alzheimer’s disease) or physiological brain state (fasted or satiated, awake or anesthetized, learning and memory et al) by using electrophysiological recording, behavioral studies, immunohistological chemistry, neural tracing and microdialysis. The details are as follows:1) The LFP signals of bilateral OBs in APP/PS1and wild type mice were studied. The coherence of the bilateral LFPs in all four frequency bands (2-12Hz,12-35Hz,35-60Hz, and60-100Hz) are reduced in AD mice under spontaneous state, while only coherence in beta band was decreased in AD mice after odor stimulation. The results implied that the coherence between the two OBs in the beta band may provide some useful information in the diagnosis of AD.2) Based on the LFPs recorded from OB, c-fos and p-CREB immunohistological chemistry, we found that after NAPE administration, the basal and odor evoked activities of OB were both decreased, and the exploratory sniffing was reduced significantly. To further clarify the mechanism under this hypoactivity, we used microdialysis to measure the changes of neurotransmitters, and found that it was mainly through increasing the inhibitory neurotransmitter-GABA level.3) By comparing the power and coherence of bilateral OB LFPs in C57BL/6J mice under awake and anesthetized states, we found that the low gamma oscillations were changed both in power and coherence after anesthesia. Furthermore, ablating the centrifugal projection by anterior commissure lesion, we found that both the power and coherence were increased. This implied that the low gamma oscillations were more sensitive to brain state changes than the high gamma oscillations and centrifugal projection decreased the power and coherence of gamma bands under normal awake state.4) The LFP recording from the bilateral OBs were obtained before and after the mice learned the "Go/No-go" odor-discrimination task. We found that the power and coherence for both spontaneous and odor evoked activities in beta and low gamma bamds were changed significantly after learning, and cholinergic modulation plays an important role in the odor-associated reward. This study provided some evidence about how the OB encodes odor information both related and unrelated to reward, and confirmed that the functional connectivity between the two OBs could be modulated by odor-associated learning process.