{"title":"Nicotine enhances object recognition memory through activation of the medial prefrontal cortex to the perirhinal cortex pathway","authors":"Hirohito Esaki , Kanta Imai , Keisuke Nishikawa, Naoya Nishitani, Satoshi Deyama, Katsuyuki Kaneda","doi":"10.1016/j.neuint.2025.105963","DOIUrl":null,"url":null,"abstract":"<div><div>Nicotine enhances recognition memory across species; however, the underlying neuronal mechanisms remain incompletely understood. Our previous study using a novel object recognition (NOR) test and electrophysiological recordings of mouse brain slices demonstrated that nicotine enhanced object recognition memory by stimulating nicotinic acetylcholine receptors in the medial prefrontal cortex (mPFC). To elucidate this further, we conducted the NOR test combined with pharmacology, chemogenetics, optogenetics, and <em>ex vivo</em> electrophysiology in male C57BL/6J mice. Chemogenetic inhibition of mPFC excitatory neurons suppressed nicotine-induced enhancement of object recognition memory, whereas their activation alone was sufficient to enhance memory. Anatomical studies indicate that the mPFC sends projections to the perirhinal cortex (PRH), a brain region involved in object recognition memory. Therefore, we focused on mPFC-PRH projections. Whole-cell patch-clamp recordings with optogenetic stimulation revealed that PRH pyramidal neurons received monosynaptic and glutamatergic inputs from the mPFC. Chemogenetic suppression of mPFC neurons projecting to the PRH blocked the nicotine-induced enhancement of object recognition memory, whereas activation of these neurons alone was sufficient to enhance memory. To achieve precise temporal control, optogenetic inhibition of the mPFC-PRH pathway during the training session blocked the effects of nicotine, and its activation alone enhanced memory. Furthermore, unilateral intra-mPFC nicotine infusion enhanced object recognition memory, and this effect was suppressed by ipsilateral intra-PRH infusion of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist. These findings indicate that nicotine enhances object recognition memory by activating glutamatergic projections from the mPFC to PRH.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105963"},"PeriodicalIF":4.4000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemistry international","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0197018625000361","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Nicotine enhances recognition memory across species; however, the underlying neuronal mechanisms remain incompletely understood. Our previous study using a novel object recognition (NOR) test and electrophysiological recordings of mouse brain slices demonstrated that nicotine enhanced object recognition memory by stimulating nicotinic acetylcholine receptors in the medial prefrontal cortex (mPFC). To elucidate this further, we conducted the NOR test combined with pharmacology, chemogenetics, optogenetics, and ex vivo electrophysiology in male C57BL/6J mice. Chemogenetic inhibition of mPFC excitatory neurons suppressed nicotine-induced enhancement of object recognition memory, whereas their activation alone was sufficient to enhance memory. Anatomical studies indicate that the mPFC sends projections to the perirhinal cortex (PRH), a brain region involved in object recognition memory. Therefore, we focused on mPFC-PRH projections. Whole-cell patch-clamp recordings with optogenetic stimulation revealed that PRH pyramidal neurons received monosynaptic and glutamatergic inputs from the mPFC. Chemogenetic suppression of mPFC neurons projecting to the PRH blocked the nicotine-induced enhancement of object recognition memory, whereas activation of these neurons alone was sufficient to enhance memory. To achieve precise temporal control, optogenetic inhibition of the mPFC-PRH pathway during the training session blocked the effects of nicotine, and its activation alone enhanced memory. Furthermore, unilateral intra-mPFC nicotine infusion enhanced object recognition memory, and this effect was suppressed by ipsilateral intra-PRH infusion of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist. These findings indicate that nicotine enhances object recognition memory by activating glutamatergic projections from the mPFC to PRH.
期刊介绍:
Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.