OLFACTORY DYSFUNCTION–INDUCED RECOGNITION MEMORY IMPAIRMENT AND ITS AMELIORATION BY NICOTINE IN MICE

Olfactory dysfunction has been implicated in the onset and progression of dementia, although its mechanisms remain unclear. In contrast, nicotine has been reported to ameliorate cognitive deficits and enhance cognition. This study examined whether olfactory dysfunction induces object recognition memory impairment and evaluated the efficacy and mechanisms of nicotine. Male C57BL/6J mice received intranasal ZnSO₄ (5% in saline; 10 µL/side). Olfactory function was assessed 7 days later using the buried food-seeking test (BFT), and olfactory bulb glomerular area was analyzed histologically. Object recognition memory was evaluated using the novel object recognition test performed 5 days after ZnSO₄ administration, with the discrimination index (DI) calculated 6 h after training, and neuronal activity was assessed by c-Fos immunohistochemistry. In addition, the light-sensitive opsin CheRiff was expressed in excitatory neurons of the medial prefrontal cortex (mPFC) or dorsal hippocampus (dHPC) for optogenetic activation. ZnSO₄-treated mice showed prolonged latency in the BFT and reduced glomerular area, confirming olfactory dysfunction, along with a significant decrease in DI and reduced c-Fos expression in the mPFC and dHPC. Both the reduced DI and c-Fos expression were restored by nicotine administered before training, either systemically or locally into the mPFC or dHPC. Furthermore, optogenetic activation of the mPFC or dHPC during training improved object recognition memory in ZnSO₄-treated mice. These findings indicate that olfactory dysfunction induces object recognition memory impairment associated with reduced neuronal activity in the mPFC and dHPC, and that nicotine ameliorates this deficit by restoring activity in these regions.