David Engblom

Neural mechanisms behind reward and aversion

The goal of our research is to identify the neural circuits and the molecular mechanisms that underlie reward and aversion. In particular we are interested in the reward related signaling that is important for drug addiction, focusing on drug-induced changes in the mesolimbic dopaminergic system. We are also interested in the circuits mediating aversion in the context of drug addiction and in other disease states such as inflammatory disease and cancer. Along the same line we study other central nervous symptoms of inflammatory disease such as loss of appetite and fever. Our experiments are to a large extent carried out using genetic mouse models. In particular, we use various approaches to delete genes in specific cell types (Cre/loxP and in-vivo RNAi) and then analyze the resulting alterations in behavior and gene expression (qPCR and microarrays). When possible, we also try to validate our findings in humans.

Key publications

(for full publication list use the link in the left margin)

• Ruud J, Wilhelms DB, Nilsson A, Eskilsson A, Tang YJ, Ströhle P, Caesar R, Schwaninger M, Wunderlich T, Bäckhed F, Engblom D, Blomqvist A. (2013) Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells. FASEB J. In Press; PMID: 23395911
• Novak M, Halbout B, O’Connor E, Rodriguez J, Su T, Chai M, Crombag H, Bilbao A, Spanagel R, Stephens DN, Schütz G, Engblom D. (2010) Incentive learning underlying cocaine relapse requires mGluR5 receptors located on dopamine D1 receptor-expressing neurons. J Neurosci, 30, 11973-82
• Mameli M, Halbout B, Creton C, Engblom D, Rodriguez Parkitna J, Spanagel R, Luscher C. (2009) Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc. Nat Neurosci, 12, 1036-41.
• Bilbao A, Rodriguez Parkitna J, Engblom D, Perreau-Lenz S, Sanchis-Segura C, Schneider M, Konopka W, Westphal M, Breen G, Desrivieres S, Klugmann M, Bading H, Rodriguez de Fonseca F, Guindalini C, Vallada H, Laranjeira R, Schumann G, Schütz G, Spanagel R. (2008) Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine. Proc Natl Acad Sci U S A, 105, 17549-54.
• Engblom D, Bilbao A, Sanchis-Segura C, Dahan L, Perreau-Lenz S, Balland B, Rodriguez Parkitna J, Lujan R, Halbout B, Mameli M, Parlato R, Sprengel R, Lüscher C, Schütz G, Spanagel R. (2008) Glutamate receptors on dopaminergic neurons control the persistence of drug-seeking. Neuron, 59, 497-508.
• Lemberger T, Rodriguez Parkitna T, Chai M, Schütz G, Engblom D. (2008) CREB has a context-dependent role in activity-regulated transcription and maintains neuronal cholesterol homeostasis. FASEB J, 22, 2872-9.
• Engblom D, Kornfeld J-W, Schwake L, Tronche F, Reimann A, Beug H, Hennighausen L, Moriggl R, Schütz G. (2007) Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression. Genes Dev, 21, 1157-62.
• Engblom D, Saha S, Engström L, Westman M, Audoly L P, Jakobsson J, Blomqvist A. (2003) Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis. Nat Neurosci, 6, 1137-38.
• Ek M, Engblom D, Saha S, Blomqvist A, Jakobsson P-J and Ericsson-Dahlstrand A (2001) Pathway across the blood-brain barrier. Nature, 22;410, 430-1.