Chronic nicotine enhances object recognition memory via inducing long-term potentiation in the medial prefrontal cortex in mice

Abstract

Chronic nicotine administration enhances cognitive functions, including learning and memory, and ameliorates cognitive impairments observed in psychological and neurodegenerative disorders. However, the detailed mechanisms underlying these effects are not fully understood. In this study, we used a novel object recognition (NOR) test and in vitro slice electrophysiology in mice to investigate the involvement of the medial prefrontal cortex (mPFC), a brain region connected to the hippocampus, and the synaptic plasticity within this region in chronic nicotine-induced object recognition memory enhancement. The NOR test revealed that chronic nicotine administration for five consecutive days significantly enhanced object recognition memory in male and female mice. This effect was blocked by intra-mPFC infusion of mecamylamine (Mec), a non-selective nicotinic acetylcholine receptor (nAChR) antagonist. In parallel with these findings, whole-cell recordings demonstrated that chronic nicotine administration significantly increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-d-aspartate (NMDA) ratio in mPFC layer V pyramidal neurons in male but not female mice. This plastic change was suppressed by systemic injection of Mec or methyllycaconitine, an α7 nAChR antagonist. Furthermore, optogenetic erasure of long-term potentiation (LTP) through chromophore-assisted light inactivation of cofilin, a protein essential for stabilizing spine expansion, suppressed chronic nicotine-induced enhancement of recognition memory. These findings suggest that chronic nicotine administration induces LTP in mPFC pyramidal neurons, likely enhancing object recognition memory.