Plasticity in the Temporal Lobe: Involment of Acetylcholine and NGF Signaling

• Antragsteller: Professor Dr. Oliver von Bohlen und Halbach; Professor Dr. Klaus Unsicker
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2010 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 168859973

Several lines of evidence suggest that acetylcholine (ACh) and the neurotrophins profoundly affect neuronal plasticity in the hippocampus and neocortex. The cholinergic system is crucially involved in learning and in short- and long-term memory. Signaling by BDNF and its receptor trkB has been shown by several laboratories, including ours, to play important roles in neuronal plasticity, both under physiological and pathophysiological conditions. However, an involvement of the prototypic neurotrophin nerve growth factor (NGF) and its receptors trkA and p75NTR in these functions has not been profoundly investigated. We propose to examine the impact of NGF-signaling on neuronal plasticity in the amygdala and hippocampus on both morphological and electrophysiological levels. We shall use heterozygote trkA and conditional trkA (trkAlox/lox;NesCre+/-) deficient mice as well as p75NTR deficient mice (p75NTRExonIII and p75NTRExonIV). We shall focus on quantitative morphological analyses of cholinergic systems (cell bodies, fibers spines), postnatal neurogenesis in the dentate gyrus, and electrophysiological parameters, as e.g., LTP, LTD, PPF, und persistent activity. In cooperation with the ZI Mannheim we shall conduct behavioral analyses. Beyond the immediate results obtained we expect advances in better understanding of mechanisms underlying several neuropsychiatric deficits, such as impaired memory and depression.

• DFG-Verfahren: Sachbeihilfen