Scientists claim to have visualized for the first time the cellular process of memory formation in rats. Gary Lynch and colleagues at the University of California (Irvine) and Carnegie Mellon University (Pittsburgh, PA) used microscopic technology and a special marker to observe memory-related changes in the synapses of rat brains.

A process called long-term potentiation (LTP) underlies these synapse changes. LTP is a transient increase in the strength of a synapse that is thought to contribute to memory formation and storage. Lynch's lab previously showed that induction of LTP in vitro was accompanied by a marked, temporary increase in the phosphorylation of cofilin, an actin-binding protein, in dendritic spines of the potentiated synapses. Now, the group has used cofilin phosphorylation as a biochemical marker of LTP induction in vivo.

Lynch and colleagues allowed one group of rats to explore a new environment and compared them with another group of rats that did not explore. After killing the rats, they measured cofilin phosphorylation in the hippocampus (J. Neurosci. 27, 8031–8039; 2007). The explorer rats had 30% more dendritic spines with phosphorylated cofilin than the other group. The incidence of spines containing phosphorylated cofilin was low overall (∼1 in 300). The hippocampal synapses with the LTP marker were 50% larger than those without.

The connection between memory and phosphorylated cofilin (and, by extension, LTP) was reinforced by results from rats that were given an NMDA receptor antagonist, which blocks the LTP process, before exploring. This treatment eliminated both memory formation and the increase in spines bearing phosphorylated cofilin.

The authors concluded that the links between phosphorylated cofilin and LTP, and between LTP and memory, suggest that the synapse changes observed in the study are directly related to the encoding of new information. They note that other mechanisms are probably responsible for long-term storage of that information.

Their ability to identify the few spines that change among the many that do not might be the first step toward mapping a complete memory circuit, a fundamental objective in learning and memory research. This goal will require even more powerful techniques, including the abilities to look at larger fields in more animals, and to look at later events. Lynch and his group now plan to apply this technique to identifying other areas of the brain that might be involved in memory.