Molecular Basis for Brain Information Storage

The major thrust of our research is to understand the molecular mechanisms underlying memory formation.

The hippocampus is one critical region for memory storage processes. Using hippocampal long-term potentiation, an electrophysiological model of memory storage, we have identified certain molecules that are essential for enhanced synaptic communication. One of these is protein kinase C, a family of enzymes associated with signal transduction and transmembrane signaling. Its substrate, GAP43, is now known to regulate axonal and synaptic growth during development and the axonal outgrowth during regeneration, and in our proposed hypothesis, during memory formation. Indeed, we now believe that GAP-43 is necessary for memory formation.

After cloning GAP-43, we have demonstrated altered gene expression of both mRNA and primary transcript during synaptic plasticity. We can induce the mRNA of this target gene in hippocampal granule cells (they normally do not synthesize GAP-43 mRNA) leading to growth of the axons of these cells, forming new connections in the adult nervous system. These genomic mechanisms regulating this growth are a target for our current investigations using the transgenic mouse that overexpresses GAP-43. Phenotypes studied for learning and memory and for synaptic plasticity indicate that the PKC site on GAP-43 regulates these fundamental brain processes

Kleschevnikov, A. and Routtenberg, A. (2001) PKC activation rescues LTP from NMDA receptor blockade. Hippocampus, in press.

Routtenberg, A., Serrano, P., Cantallops, I., Zaffuto, S. Namgung, U. (2000) Enhanced learning by genetic overexpression of a brain growth protein. Proc Nat. Acad. Sci., 97: 7657-7662.

Routtenberg, A. (1999) Tagging the Hebb synapse. Trends Neurosci., 22:255-256.

View all publications by publications by Aryeh Routtenberg listed in the National Library of Medicine (PubMed).