Prefrontal cortex, dorsomedial striatum, and dentate gyrus are necessary in the object-based attention test in mice

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: Attention; Dentate gyrus; Lesion; OBAT; Prefrontal cortex; Striatum; c-Fos.

Fig. 1

Prefrontal cortex, dorsomedial striatum, and dentate gyrus are necessary for the regulation of attention in the OBAT. a OBAT. b The representative images and number of c-Fos-positive cells in the PFC of control and PFC lesioned-mice after the OBAT. c The performance of control and PFC lesioned-mice in the OBAT. d The representative images and number of c-Fos-positive cells in the DMS of control and DMS lesioned-mice after the OBAT. e The performance of control and DMS lesioned-mice in the OBAT. f The representative images and number of c-Fos-positive cells in the DG of control and DG lesioned-mice after the OBAT. g The performance of control and DG lesioned-mice in the OBAT. *p < 0.05, **p < 0.01. n = 6–8 mice each group. Plot data indicate each mouse’s performance. Scale bar indicates 100 μm. The data are expressed as mean ± SEM