Differential environmental regulation of neurogenesis along the septo-temporal axis of the hippocampus Arnaud Tanti a, b, * , Quentin Rainer a, b , Frederic Minier a, b , Alexandre Surget a, b, c , Catherine Belzung a, b a U 930, Inserm, Tours F-37200, France b Université François Rabelais, Tours F-37200, France c Kavli Institute for Systems Neuroscience & Centre for the Biology of Memory, Norwegian University of Science and Technology (NTNU), Trondheim, Norway article info Article history: Received 24 August 2011 Received in revised form 16 April 2012 Accepted 19 April 2012 Keywords: Chronic stress Environmental enrichment Neurogenesis Fluoxetine Dorsal hippocampus Ventral hippocampus abstract The hippocampus is involved in both cognitive and emotional processing; these different functions are topographically distributed along its septo-temporal axis, the dorsal (septal) hippocampus being pref- erentially involved in cognitive processes such as learning and memory while the ventral (temporal) hippocampus participates in emotional regulation and anxiety-related behaviors. Newborn hippocampal neurons become functionally integrated into hippocampal networks and are likely to contribute to hippocampal functions, but whether their regulation and function are homogenous throughout this axis is not clear. Here we investigate changes in cell proliferation and neurogenesis along the septo-temporal axis of the hippocampus induced by the Unpredictable Chronic Mild Stress model of depression (UCMS), chronic fluoxetine treatment and enriched environment. Mice were either subjected to UCMS, standard housing or enriched environment. Stress-exposed mice were treated daily with fluoxetine (10 mg/kg) or vehicle. Effects of UCMS regimen, fluoxetine treatment and enrichment were assessed by physical measures and behavioral testing. Quantitative changes in cell proliferation and neurogenesis were assessed by immunohistochemistry using BrdU labeling. Results indicate that UCMS decreased cell proliferation and neurogenesis preferentially in the ventral hippocampus, an effect that was reversed by fluoxetine treatment. Environmental enrichment on the other hand increased cell proliferation in both divisions but promoted neurogenesis only in the dorsal hippocampus. These results indicate that environmental factors can differentially regulate neurogenesis in a region-specific manner. This may possibly underlie heterogeneous function of newborn neurons along the septo-temporal axis of the hippocampus and have functional significance as to their impli- cation in stress related disorders and memory processes. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Along its well-known role in learning and memory, the hippo- campus is involved in the regulation of motivational behaviors, emotional states and stress response. The sub-areas involved in these hippocampal functions seem however topographically segregated along its septo-temporal axis. In particular, the dorsal part of the hippocampus has been described as preferentially involved in learning and memory processes whereas the ventral hippocampus has been involved in anxiety-related behaviors and emotions (Bannerman et al., 2004; Moser and Moser, 1998). Several anatomical and physiological properties could account for these functional differences. For instance, dorsal and ventral poles do not share the same afferent and efferent connectivity. In rodents, afferences related to visuo-spatial information coming from primary sensory and associative cortex are found predominantly in the dorsal hippocampus, suggesting a preferential involvement in spatial and contextual processing (Amaral and Witter, 1989; Burwell and Amaral, 1998; Dolorfo and Amaral, 1998; Insausti et al., 1997). By contrast, reciprocal connections shared by the hippocampus with structures involved in emotional regulation such as the limbic system, the prefrontal cortex, or sub-limbic structures participating in stress integration are found predominantly in its ventral pole (Barbas and Blatt,1995; Canteras and Swanson,1992; Petrovich et al., 2001; Pitkanen et al., 2000; Swanson and Cowan, 1977). Further, a molecular heterogeneity has been described as several genes are differentially expressed and regulated along the septo-temporal axis of the hippocampus (Leonardo et al., 2006; Thompson et al., 2008). Dorsoventral differences in neurotransmission have also been reported (Gage and Thompson, 1980) as well as differences in * Corresponding author. Université François Rabelais, Faculté des Sciences et Techniques, Parc Grandmont, F-37200 Tours, France. Tel.: þ33 2 47 36 70 01. E-mail address: arnaud.tanti@etu.univ-tours.fr (A. Tanti). Contents lists available at SciVerse ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm 0028-3908/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropharm.2012.04.022 Neuropharmacology 63 (2012) 374e384