SFB 636:  Learning, Memory and Brain Plasticity: Implications for Psychopathology

• Subject Area: Medicine ; Social and Behavioural Sciences
• Term: from 2004 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5485966

The goal of this Collaborative Research Centre is to determine the specific learning processes that play a role in major mental disorders and to examine the behavioural, neural and molecular mechanisms underlying them. The basic tenet of this research is that learning processes associated with aversive life events lead to maladaptive plastic changes in the brain that underlie the various disease symptoms in conjunction with genetic predispositions. Special emphasis will be put on the characterisation of both behavioural and neurobiological variables of learning, memory and brain plasticity and their interaction. We believe that both neurobehavioural and molecular mechanisms must be separately assessed and their interrelationships specified.
Although we will use formal DSMIV and ICD diagnoses in the clinical projects the aim of our research is to identify neurobiological and neurobehavioural mechanisms of learning and plasticity across several disorders and to determine to what extent similarities and differences between disorders exist. This approach also permits more specific analyses of molecular mechanisms that have so far suffered from the large and often diverse number of symptoms classified under one diagnostic category. In addition, treatment implications of these learning-induced memory traces will be examined and the effects of various treatments on brain plasticity and characteristics of learning will be studied. Whereas disorders of sensory and motor processing such as chronic pain, tinnitus or dystonia have been found to be associated with plastic learning-related changes in the primary sensory and motor areas of the cortex, we assume that changes associated with disorders that involve mainly emotional and motivational problems are primarily associated with alterations in subcortical, limbic and frontal areas. We have therefore focused our research efforts on those disorders where we believe both associative and nonassociative learning processes and concomitant plastic alterations of the brain to be of special importance: anxiety disorders, disorders of affect regulation, affective disorders and addiction.
The ultimate goal of this research effort is the exact description of the behavioural, neural and molecular deviations in associative and nonassociative learning related to these disorders as well as the development of new assessment and mechanism-based behavioural and pharmacological treatment approaches.

• DFG Programme: Collaborative Research Centres
• International Connection: USA

Completed projects

• A01 - L-type voltage gated calcium channel Cav1.3á1(á1D): role in memory extinction and synaptic plasticity (Project Head Bartsch, Dusan )
• A02 - Stem cell-derived neurons: a model to study the impact of neurotrophins and glia-derived neuroprotective factors on serotonergic neuron (Project Head Schloss, Patrick )
• A03 - Molecular analysis of glucocorticoid action underlying hippocampal neurogenesis and synaptic plasticity (Project Head Schütz, Günther )
• A04 - The role of NMDA and AMPA receptors of excitatory neurons in hippocampal based memories (Project Head Sprengel, Rolf )
• A05 - Plasticity in the temporal lobe: Involvement of acetylcholine and NGF signaling (Project Heads von Bohlen und Halbach, Oliver ;  Unsicker, Klaus )
• A06 - The role of the NMDA receptor- and nuclear calcium-regulated de novo DNA methyltransferase Dnmt3a2 in the consolidation and extinction of hippocampal dependent memory. (Project Head Bading, Hilmar )
• A07 - Long-term memory extinction/reconsolidation in Drosophila: Characterization of cellular signaling pathways, underling neuronal networks and molecular mediators (Project Heads Bading, Hilmar ;  Schuster, Christoph M. )
• B01 - Reconsolidation of alcohol-associated memories: From underlying cellular mechanisms to glutamatergic interventions (Project Head Spanagel, Rainer )
• B02 - Molecular mechanisms of neural and synaptic plasticity in models of depression (Project Heads Gebicke-Härter, Peter Joachim ;  Henn, Fritz A. ;  Rietschel, Marcella ;  Thome, Johannes )
• B03 - Profiling stress effects, environment and drug action using glucocorticoid receptor (GR) reporter mice (Project Head Gass, Peter )
• B05 - Demonstration of structural and functional connectivity changes in patients with memory and motor dysfunction in subcortical vascular encephalopathy (Project Heads Gass, Achim ;  Hennerici, Michael )
• B06 - Coordinated network activity in the hippocampus: effects of glucocorticoids and stress on assembly formation and propagation (Project Heads Both, Martin ;  Draguhn, Andreas )
• B07 - Plasticity in prefrontal circuits in the human: Genetic variation, cellular mechanisms, and neurofeedback modulation (Project Heads Meyer-Lindenberg, Andreas ;  Rietschel, Marcella ;  Utikal, Jochen )
• B08 - Phasic dopamine-modulation of spike-timing-dependent plasticity and its implications for associative learning (Project Heads Durstewitz, Daniel ;  Kelsch, Wolfgang )
• B09 - Mechanisms underlying structural plasticity during memory consolidation in forebrain circuits (Project Heads Kuner, Rohini ;  Kuner, Thomas )
• C01 - Learning and brain plasticity in posttraumatic stress disorder: determinants of risk and the role of cue and context conditioning (Project Head Flor, Herta )
• C02 - Learning and brain plasticity in borderline personality disorder with and without comorbid posttraumatic stress disorder (Project Head Bohus, Martin )
• C03 - Acquisition, retrieval and extinction of fear memories in social phobia: Neuronal correlates and modulating factors (Project Heads Hermann, Christiane ;  Schad, Lothar Rudi )
• C05 - Impact of cognitive and sensory information processing during reconsolidation of fear-memory in humans (Project Heads Bohus, Martin ;  Schmahl, Christian )
• C06 - Reward sensitivity and reinforcement learning in bipolar disorder: state dependency and diagnostic specificity (Project Head Wessa, Michèle )
• C07 - Implicit and explicit learning and memory processes in acute and chronic hippocampal impairment: The role of stress (Project Heads Gass, Achim ;  Hennerici, Michael ;  Nees, Frauke ;  Szabo, Kristina )
• D01 - Measuring neuronal plasticity during treatment of affective disorders (Project Heads Ende, Gabriele ;  Henn, Fritz A. )
• D04 - Modulation of appetitive and aversive associative learning in major depressive disorder (Project Heads Diener, Carsten ;  Kühner, Christine )
• D05 - Declarative memory deficits and their neurobiological basis in the course of major depression (Project Head Weisbrod, Matthias )
• D06 - Reward learning and extinction training in alcohol dependence: impact of fronto-striatal connectivity (Project Heads Kiefer, Falk ;  Kirsch, Peter )
• D07 - Neuroplasticity of brain glutamate and glutamine and treatment response in alcoholism: A translational MR spectroscopy study (Project Heads Ende, Gabriele ;  Mann, Karl ;  Sommer, Wolfgang Heinrich )
• D08 - Does learning of self-regulation normalize reward-processing and performance monitoring in ADHD? (Project Heads Banaschewski, Tobias ;  Brandeis, Daniel ;  Holtmann, Martin )
• MGK - Integrated research training group: Translational Neurosciences (Project Heads Draguhn, Andreas ;  Flor, Herta ;  Spanagel, Rainer )
• Z01 - Central tasks of the Collaborative Research Center (Project Head Flor, Herta )
• Z03 - Diffusor tension imaging tractography, brain network analysis and advanced translational magnetic resonance imaging /magnetic resonance spectroscopy methods (Project Heads Ende, Gabriele ;  Schad, Lothar Rudi )
• Z04 - Molecular genetic core facility for genotype-phenotype delineation (Project Heads Rietschel, Marcella ;  Witt, Stephanie )

• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Participating Institution: Deutsches Krebsforschungszentrum (DKFZ); Max-Planck-Institut für medizinische Forschung; Zentralinstitut für Seelische Gesundheit (ZI)
• Spokesperson: Professorin Dr. Herta Flor