Effects Of Enriched Odor Exposure On Learning And Memory And The Underlying Mechanisms

[Background]Olfactory plays an important role in the physiological function in mammalians. Olfactory neurons project axons to various brain regions including amygdala and hippocampus, both of them are essential for the learning and memory. Therefore, olfactory system not only correlative with olfactory function, but also with learning and memory function. Environmental enrichment is a commonly used experimental paradigm known to improve brain cognitive function through the enhancement of neuronal plasticity, learning, memory, and neurogenesis in the adult brain. But how odor enrichment could affect the learning and memory is still not clear.[Objective]It was to study the effects of enriched odor exposure on learning and memory and underlying mechanisms.[Methods]We carried out three independent environments:1) Control, normal environment without extra odor exposure.2) Pleasant odor exposure, an odor exposure environment fill of a single odor that rats like 3) Disgust odor exposure environment, an odor exposure environment fill of a single odor that rat dislike. Adult male Sprague Dawley rats aged 8 weeks were randomly assigned to four experimental groups:1) Control group, housed in the control environment; 2) Enriched odor exposure group, randomly housed in the pleasant odor exposure or disgust odor exposure environment and odor exposure environment replace ever 24-48h; 3) Pleasant odor exposure group, housed in the pleasant odor exposure environment 4) Disgust odor exposure group, housed in the disgust odor exposure environment. The enriched odor exposure group consisted of rats housed in an odor exposure environment for 40 d as a short-term exposure or 80 d as a long-term exposure and exposed daily for 24 hr to different odors which replace ever 24 h. After enrichment, Morris Water maze and Fear conditioning task was used to examine the effects of enriched odor exposure on hippocampus dependent learning/memory and emotional memory, respectively. Golgi staining was used to examine the the shape and morphology of spine. Western blotting and Immunohistochemistry was applied to detect the expressions and activities of presynaptic proteins, postsynaptic proteins, synaptic kinases and memory-associated signals.[Results]1) Short-term enriched odor exposure improves hippocampus dependent spatial learning and emotional memory but not memory, with increased the number of thin dendritic spines and total spines. Short-term enriched odor exposure also increased the levels of presynaptic protein synapsin I, synaptophysin and caused synapsin I phosphorylation by activation of cAMP-dependent protein kinase (PKA). Long-term enriched odor exposure improves hippocampus dependent spatial learning/memory and emotional memory, with increased the number of thin spines, mushroom dendritic spines and total spines. Long-term enriched odor exposure also increased the protein levels of presynaptic protein synapsin I, synaptophysin, postsynaptic proteins PSD93, PSD95 and caused cAMP response element binding (CREB) and synapsin I phosphorylation by activation of calmodulin-dependent protein kinaseâ…¡(CaMKII).2) Pleasant odor short-term exposure improves hippocampus dependent spatial learning/memory and emotional memory, with increased the protein levels of presynaptic protein synapsin I, synaptophysin, postsynaptic proteins PSD93. PSD95 and with activation of PKA, CaMKII and CREB. Disgust odor short-term exposure improves hippocampus dependent spatial learning but impairs emotional and spatial memory, with increased the protein levels of presynaptic protein synapsin I, synaptophysin, decreased the protein levels of postsynaptic proteins PSD93, PSD95. It is also increased the activation of PKA and prorein phosphatase type 2A (PP2A), decreased the activation of CaMKII.3) Pleasant odor long-term exposure improves hippocampus dependent spatial learning/memory and emotional memory, with increased the protein levels of presynaptic protein synapsinâ… , synaptophysin, postsynaptic proteins PSD93, PSD95 and with activation of CaMKII and CREB. Disgust odor short-term exposure improves hippocampus dependent spatial learning/memory but impairs emotional memory, with increased the protein levels of presynaptic protein synapsin I, synaptophysin, postsynaptic proteins PSD93, PSD95 and with activation of CaMKII and CREB. It is also decreased the activation of GSK-3[Conclusions]Enriched odor exposure could improve spatial learning/memory and emotional memory. Short-term and long-term enriched odor exposure time differentiated improves spatial learning and/or memory by activating PKA and CaMKII/CREB synaptic signals, respectively. Pleasant odor exposure could improve emotional memory, and improve spatial learning and memory by activating PKA and CaMKII/CREB synaptic signals in short-term enrichment. In long-term enrichment, it improves learning and memory only by activating CaMKII/CREB synaptic signals. Disgust odor exposure impair emotional and spatial memory by activating PP2A and inactivating CaMKII in short-term enrichment, but in long-term enrichment, it could improve spatial learning by activating PKA, and improve spatial memory by activating CaMKII and inactivating GSK-3.