Why am I lost without dopamine? Effects of 6-OHDA lesion on the encoding of reward and decision process in CA3 Aude Retailleau a,b , Cyril Dejean c,d , Benjamin Fourneaux a,b , Xavier Leinekugel a,b , Thomas Boraud a,b, ⁎ a University of Bordeaux, Institut des Maladies Neurodegeneratives UMR 5293, Bordeaux, France b CNRS, Institut des Maladies Neurodegeneratives UMR 5293, Bordeaux, France c University of Bordeaux, Institut de Neurosciences Cognitives et Integratives d'Aquitaine UMR 5287, Bordeaux, France d CNRS, Institut de Neurosciences Cognitives et Integratives d'Aquitaine UMR 5287, Bordeaux, France abstract article info Article history: Received 15 May 2013 Revised 24 June 2013 Accepted 24 July 2013 Available online 1 August 2013 Keywords: Spatial navigation Hippocampus Monoamine Electrophysiology Behavioral studies Rats There is growing evidence that Parkinson's disease, generally characterized by motor symptoms, also causes cog- nitive impairment such as spatial disorientation. The hippocampus is a critical structure for spatial navigation and receives sparse but comprehensive dopamine (DA) innervation. DA loss is known to be the cause of Parkinson's disease and therefore it has been hypothesized that the associated spatial disorientation could result from hippo- campal dysfunction. Because DA is involved in the prediction of reward expectation, it is possible to infer that spatial disorientation in DA depleted subjects results from the loss of the ability to detect the rewarding features within the environment. Amongst hippocampal formation subdivisions, CA3 properties such as the high liability of its place fields make it a serious candidate for interfacing DA reward system and spatial information encoding. We addressed this issue using multiple electrode recordings of CA3 in normal and dopamine depleted rats performing a spatial learning in a Y-maze. Our data confirm that DA is essential to spatial learning as its depletion results in spatial impairments. The present work also shows that CA3 involvement in the detection of spatial fea- ture contextual significance is under DA control. Finally, it also shows that CA3 contributes to the decision making processes of navigation tasks. The data also reveal a lateralization effect of DA depletion underlined by neural correlates. © 2013 Elsevier Inc. All rights reserved. Introduction Parkinson's disease (PD) is a neurological disorder characterized by the manifestation of motor symptoms, attributed to the degeneration of dopamine (DA) neurons of the substantia nigra pars compacta (SNc) (Ehringer and Hornykiewicz, 1960). Nevertheless, beside PD motor symptoms that are well defined and controlled by pharmacological therapies, this condition is also characterized by cognitive impairments and most notably a form of spatial disorientation, a dysfunction, in which the hippocampus is implicated (Pillon et al., 1996; Shohamy et al., 2005). It was thought that cognitive impairments are present in 30% of PD patients, appear lately and are correlated with cortical atro- phy. Recent investigations modified this assumption: a recent epidemi- ological meta-study established that cognitive impairments appear early in 15–20% of PD patients and will eventually be present in 70 to 80% of the patients (Svenningsson et al., 2012). An fMRI protocol showed correlation between subcortical dysfunction at hippocampal and striatal level and the cognitive impairment (Weintraub et al., 2011). Numerous theories of hippocampal function have been advanced over the past decades, and a general agreement has been reached that this structure plays a role in memory, and especially in spatial memory. Several studies report that hippocampal lesions in rats lead to severe deficits in tasks requiring spatial information (Barnes, 1988; Morris et al., 1982; O'Keefe et al., 1975; Poucet and Benhamou, 1997; Sutherland et al., 1982). Nevertheless, the main argument in favor of a spatial function for the hippocampus was the discovery of place cells. More than 35 years ago, O’Keefe and Dostrovsky (1971) reported that neuronal discharge was correlated to the position of the animal in the environment. These cells are pyramidal cells (Henze et al., 2000; O’Keefe, 1979) localized in CA1 and CA3 areas of hippocampus. Dopaminergic afferents to the hippocampal formation arise from both the ventral tegmental area (VTA, A10) and substantia nigra pars compacta (SNc, A8-A9) dopaminergic cell groups (Scatton et al., 1980). In addition, intra-hippocampal injections of D1 agonists and D2 antagonists improve memory (Packard and White, 1991; Wilkerson and Levin, 1999), while 6-OHDA lesions of dopaminergic inputs to hip- pocampus result in spatial working memory deficits (Gasbarri et al., 1996). The dorsal part of CA3, which is considered to be involved in the rapid acquisition of new memory (Kesner, 2007), is the target of DA projections from VTA and SNc (Luo et al., 2011; Scatton et al., 1980). DA innervation together with a higher liability of place fields as Neurobiology of Disease 59 (2013) 151–164 ⁎ Corresponding author at: CNRS, Institut des Maladies Neurodegeneratives UMR 5293, Bordeaux, France. E-mail address: tboraud@u-bordeaux2.fr (T. Boraud). Available online on ScienceDirect (www.sciencedirect.com). 0969-9961/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.nbd.2013.07.014 Contents lists available at ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi