Prefrontal cortex, dorsomedial striatum, and dentate gyrus are necessary in the object-based attention test in mice
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Prefrontal cortex, dorsomedial striatum, and dentate gyrus are necessary in the object‑based attention test in mice Bolati Wulaer1,2 , Kazuo Kunisawa3 , Hisayoshi Kubota3 , Willy Jaya Suento2,4 , Kuniaki Saito2,5 , Akihiro Mouri3,5* and Toshitaka Nabeshima1,5
Abstract Disturbances of attention are a common behavioral feature associated with neuropsychiatric disorders with largely unknown underlying causes. We previously developed an object-based attention test (OBAT) as a simple and practical method for evaluating attention in mice. Since its establishment, the test has become a popular method for assessing attention and related underlying mechanisms in various mouse models. However, the underlying neuronal network involved in this test has yet to be studied. The purpose of this study was to identify the principal brain regions activated in the OBAT. Accordingly, C57BL/6J mice were subjected to the OBAT and thereafter prepared for immunohistochemical quantification of c-Fos, an immediate early gene that is frequently used as a marker of neuronal activity, in 13 different brain regions. The number of c-Fos-positive cells was significantly higher in the prefrontal cortex (PFC), dorsomedial striatum (DMS), and dentate gyrus (DG) in the test group as compared to the control group. The neuronal activation of these brain regions during the OBAT indicates that these brain regions are necessary for the regulation of attention in this test. This was supported by excitotoxic lesioning of these brain regions, leading to impaired attention without causing locomotor dysfunction. This study is one of the first attempts to analyze the brain regions that regulate attention in the OBAT. These findings provide an initial insight into the role of these brain regions and ideas for studying the underlying neural and molecular mechanisms. Keywords: Prefrontal cortex, Striatum, Dentate gyrus, Attention, OBAT, c-Fos, Lesion Main text Attention plays a critical role in cognition. Impaired attention is often seen in patients with various neuropsychiatric disorders, such as attention-deficit hyperactivity disorder (ADHD), schizophrenia, and major depressive disorder [1–3]. We have previously developed an objectbased attention test (OBAT) as a simple and practical method suitable for the evaluation of attention in mice *Correspondence: mouri@fujita‑hu.ac.jp 3 Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, 1‑98 Dengakugakubo, Kutsukake‑cho, Toyoake, Aichi 470‑192, Japan Full list of author information is available at the end of the article
[4]. This behavioral test relies on mice’s inherent behavior to explore novelty in the absence of any instrumental training or external reinforcers. The test comprises two phases: training (familiarization) and testing. In the training session, mice are presented with five different shaped but similarly sized objects for familiarization; a novel and familiar object are
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