Reversible olfactory dysfunction impaired learning and memory with impaired hippocampal synaptic plasticity and increased corticosterone release in mice.

Olfactory dysfunction is related with various neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease and Parkinson's disease, which show impaired cognitive functions. However, the effects of olfactory dysfunction on hippocampal dependent learning and memory remain elusive. In this study, mice were treated with intranasal zinc sulfate (ZnSO4) infusion which resulted in a complete but reversible loss of olfactory function. Olfaction was totally destroyed even 1 week after zinc sulfate treatment, but partially recovered 4 weeks later. We found learning and memory in Y-maze and fear conditioning were not affected by ZnSO4 1 week after the treatment, but learning and memory were severely destroyed 4 weeks later. Electrophysiology results showed impaired hippocampal long-term potentiation and long-term depression 4 weeks after the olfaction dysfunction, while only long-term depression was impaired 1 week after the treatment. Western blot showed that the expression and phosphorylation of GluA1 in zinc group did not show any increase after fear conditioning as the control mice. Serum corticosterone release was increased in olfactory deficit mice at baseline and after acute stress when tested 3, 10 and 20 days after the olfactory dysfunction. All these results indicated that reversible olfactory dysfunction elicited impaired hippocampal function in mice. The higher corticosterone release after olfactory deficiency might serve as an underling mechanism.