SFB 1080:  Molecular and Cellular Mechanisms of Neural Homeostasis

• Subject Area: Medicine
• Term: from 2013 to 2024
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 221828878

Neural homeostasis refers to one of the most remarkable features of the nervous system: its ability to maintain a balanced and stable internal state in response to a constant flow of inputs from an ever-changing environment. This continuous adaptation is ensured by homeostatic feedback mechanisms acting at the molecular, cellular and circuit levels to maintain nervous system functions around flexible set-points. Brain homeostasis is proposed to prevent damaging or inefficient states by adjusting neuronal function and keeping neurons in an optimal operating regime supporting information transfer and processing across neuronal circuits. Homeostatic adaptation is thus critical for the stability of the nervous system, while simultaneously allowing for a certain degree of structural, functional and organizational flexibility as a platform for development and adaptation to new environments and experiences. In other words, homeostatic stability and flexibility can be considered as two complementary and mutually dependent design principles of the brain. In the CRC1080 we explore the fundamental processes enabling the nervous system to maintain the functionality, adaptability and flexibility of its network components during physiological conditions, and also how these mechanisms are altered in pathological situations. We are aware that numerous mechanisms operating on different scales are involved. Therefore, our approach includes projects that analyze the molecular mechanisms of circuit maintenance through the regulation of apoptosis, neurogenesis, ribostasis and proteostasis, as well as neuronal morphology and synaptic transmission from the pre- and postsynaptic side (Areas A and B). After its implementation in the second funding period, we are now strengthening the study of the regulation of network function at a circuit level in physiological and altered conditions using experimental and computational approaches (Area C). Across all areas, we are also exploring the influence of the microenvironment on neuronal homeostasis by including non-neuronal cells (glia, endothelial cells and perivascular cells), which are newly emerging key players in the modulation of homeostatic mechanisms. Draw on the strengths of different experimental and computational approaches many of our projects search to arrive at a detailed analysis of the morphological, cellular and biochemical processes associated with homeostatic mechanisms and to elucidate the chain of events that constitutes homeostasis in the nervous system.

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

Current projects

• A01 - Activity-Dependent Regulation of Apoptosis in Developing Rodent Cerebral Cortex. (Project Heads Luhmann, Heiko J. ;  Sinning, Anne )
• A05 - Deciphering the role of Yap1 in the life-long homeostasis of hippocampal neural stem cells (Project Heads Berninger, Benedikt ;  Stroh, Albrecht ;  Tiwari, Vijay )
• A06 - Post-transcriptional mechanisms in synaptic plasticity and memory consolidation: Role of mRNA stability (Project Heads Lutz, Beat ;  Niehrs, Ph.D., Christof )
• A11 - Interaction of homeostatic challenges in activity control for dopamine substantia nigra neurons by alpha-synuclein pathology, aging and cell loss (Project Head Roeper, Jochen )
• B01 - Coordination of Protein Synthesis and Degradation in Neurons. (Project Head Schuman, Erin M. )
• B02 - Regulation of presynaptic homeostasis at the level of synaptic vesicle filling, mobilization, fusion and recycling (Project Head Gottschalk, Alexander )
• B03 - Molecular mechanisms of homeostatic neuronal adaptations after denervation. (Project Heads Deller, Thomas ;  Vlachos, Andreas )
• B04 - Molecular mechanisms regulating homeostatic changes at dendrites and dendritic spines: role of the neurovascular interface (Project Head Acker-Palmer, Amparo )
• B10 - Homeostatic regulation of mTOR dependent synaptic function (Project Heads Luhmann, Heiko J. ;  Schmeißer, Michael ;  Schweiger, Susann )
• B11 - Activity-dependent regulation of AMPA receptor function by auxiliary subunits (Project Head von Engelhardt, Jakob )
• B12 - The roles of VGCCs and Ca2+ pumps in orchestrating SV release, recycling, and presynaptic homeostatic plasticity (Project Heads Duch, Carsten ;  Heine, Martin )
• C01 - Immune Cytokines in the Regulation of Neuronal Homeostasis (Project Heads Kipnis, Jonathan ;  Vogelaar, Ph.D., Christina Francisca ;  Zipp, Frauke )
• C02 - Adaptive cellular mechanisms of functional reorganization and recovery after traumatic brain injury (TBI) (Project Heads Mittmann, Thomas ;  Tegeder, Irmgard )
• C03 - Homeostatic regulation of protein copy numbers and its impact on neural network activity (Project Head Tchumatchenko, Tatjana )
• C04 - Homeostatic regulation of REM-non REM transition in sleep (Project Head Laurent, Gilles )
• C05 - Homeostatic maintenance of neuronal function in a dynamic network. (Project Heads Loewenstein, Yonatan ;  Rumpel, Simon )
• C06 - Behavioral and circuit stability in dynamically changing visual environments (Project Head Silies, Marion )
• C07 - Homeostatic regulation of networkfunction under normal and altered sensory input (Project Head Gjorgjieva, Ph.D., Julijana )
• MGK - Integrated Research Training Group on Molecular and Cellular Mechanisms of Neural Homoeostasis (Project Heads Acker-Palmer, Amparo ;  Luhmann, Heiko J. ;  Mittmann, Thomas )
• Z - Central tasks of the CRC (Project Heads Acker-Palmer, Amparo ;  Nitsch, Robert )

Completed projects

• A02 - Bioactive Phospholipid Signaling in Homeostatic Regulation of Neuron Numbers and Connections (Project Heads Nitsch, Robert ;  Vogt, Johannes )
• A03 - EGFL7 and progranulin (PRGN) in neurogenesis: a notch above as a duo in neural homeostasis. (Project Heads Schmidt, Mirko H.H. ;  Schwarzacher, Stephan ;  Tegeder, Irmgard )
• A04 - Homeostasis of the Main Olfactory Epithelium in Mouse (Project Head Mombaerts, Peter )
• A07 - Functional role of the proteasome and autophagic protein degradation system in neuronal homeostasis following traumatic brain injury (Project Heads Behl, Christian ;  Engelhard, Kristin ;  Mittmann, Thomas )
• A08 - Stabilization of neuronal protein homeostasis by adaptation of chaperone activity to longterm proteotoxic stress in vivo (Project Heads Behl, Christian ;  Clement, Albrecht )
• A09 - Progranulin in the Adaptive Response of the Nociceptive System to Damage (Project Head Tegeder, Irmgard )
• A10 - GDAP1 is a redox sensor that controls cellular redox homeostasis by altering mitochondrial shape and function (Project Head Methner, Axel )
• B05 - Role of bioactive lipid signaling in homeostatic control of excitatory transmission. (Project Heads Huai, Ph.D., Jisen ;  Nitsch, Robert ;  Vogt, Johannes )
• B06 - Molecular mechanisms of neuronal homeostasis during inflammatory processes in the CNS (Project Heads Schäfer, Michael K. E. ;  Zipp, Frauke )
• B07 - Mechanisms of Homeostatic and Allostatic Electrophysiological States of Dopaminergic Midbrain Neurons in Aging and Models of Parkinson Disease (Project Head Roeper, Jochen )
• B08 - Endocannabinoids in negative feedback mechanisms: involvement of epigenetic mechanisms underlying homeostasis and the shift to allostasis (Project Head Lutz, Beat )
• B09 - The role of the protein receptor-mediated endocytosis 8 (RME8) in neuronal homeostasis (Project Heads Behl, Christian ;  Clement, Albrecht )

• Applicant Institution: Goethe-Universität Frankfurt am Main
• Participating University: The Hebrew University of Jerusalem; Department of Neurobiology; Johannes Gutenberg-Universität Mainz
• Participating Institution: Institut für Molekulare Biologie gGmbH; Max-Planck-Institut für Hirnforschung
• Spokespersons: Professorin Dr. Amparo Acker-Palmer; Professor Dr. Robert Nitsch, until 12/2016