Molecular mechanisms of LTP consolidation in vivo

The ability of the brain to store information stems from the fundamental plasticity of neuron-to-neuron communication at synapses. Rather than being static entities, synapses can undergo lasting increases or decreases in strength in response to specific i nput patterns. Synaptic plasticity is thought to underlie a broad range of adaptive functions in the central nervous system from memory storage to pain control. In turn, defects in synaptic plasticity play a central role in memory loss, and possibly in pa in hypersensitivity states, and susceptibility to depression. Understanding synaptic plasticity has therefore become a major goal of neuroscience. The phenomenon of long-term potentiaton (LTP) is a form of neuronal memory induced by patterned stimulation of excitatory synapses. Like consolidation of long-term memory, the stability of LTP depends on new gene expression and protein synthesis. However, the molecular mechanisms that control and shape the consolidation process are little known. This project is comprised of two interlocking subprojects on the mediation and induction of LTP consolidation in the dentate gyrus of adult rats. The core hypothesis is that translation of the dendritic mRNA species, Arc, mediates LTP consolidation, and that this proces s is triggered by activity-evoked BDNF signaling. The multidisciplinary strategy involves electrophysiological and subcellular imaging techniques combined with local pharmacological and genetic approaches in organotypic hippocampal slice-cultures and live rats.