Plasticity in the temporal lobe: Involvement of acetylcholine and NGF signaling

Several lines of evidence suggest that acetylcholine (ACh) and the neurotrophins have profound influences on neuronal plasticity in the limbic system. 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 modulation, both under physiological and pathophysiological (e.g. depression) conditions. However, an involvement of the prototypic neurotrophin nerve growth factor (NGF) and its receptors trkA and p75 in these functions has not been profoundly investigated. We propose to examine the impact of NGF-signaling on neuronal plasticity within the limbic system both on the morphological and electrophysiological levels. Several lines of evidence suggest that NGF may play a key role in the establishment as well as in the maintenance and modulation of the cholinergic system. We therefore propose to analyze the NGF-system, its impact on the adult cholinergic system, as well as on cholinergic mechanisms, involved in neuronal plasticity, learning and long- and short-term memory. We shall use trkA and conditional trkA deficient mice (trkAlox/lox;NesCre+/-) as well as p75NTR deficient mice (p75NTRExIV). Beyond understanding the roles of ACh and NGF in the limbic system and in neuronal plasticity in general, these studies may contribute to a better understanding of mechanisms underlying deficits in memory formation and depression.

Ansprechpartner: Prof. Dr. Klaus Unsicker
Tel: 0761/203-5193
Email: ku39@anat.uni-freiburg.de

Projektbeginn: 01.04.2009
Projektende: (unbegrenzt)

Unsicker K

Albert-Ludwigs-Universität Freiburg