Tsien leads study of learning and memory

July 30, 2001, 12:25 a.m.

A Princeton neurobiologist has assembled a genetic "parts list" for the brain region that controls most learning and memory. This catalog is a first step in drawing up complete plans and diagrams for how the learning and memory system works, said Assistant Professor of Molecular Biology Joe Tsien, who led the study.

In a paper published in the July 17 issue of the Proceedings of the National Academy of Sciences, Tsien reported that he and colleagues screened 33,000 genes and found 4,390 involved in constructing and operating the brain's learning and memory apparatus in mice. As in many areas of biology, researchers expect significant similarities between these functions in mice and humans.

"We are not at a stage of understanding the function of all these genes," said Tsien. "But it represents a tremendous amount of information coming from an exciting new technique."

Tsien used a device known as a GeneChip to track the activity of nearly every gene in fetal and newborn mice -- 33,000 genes and gene fragments. Each of these devices, which resemble half-inch square computer chips, holds 6,000 to 10,000 pieces of DNA. When the chip is exposed to tissue from a developing mouse, genes that are active in that tissue glow with a green fluorescent light while the inactive ones stay dark.

Tsien used GeneChips to track the activity of genes at five stages throughout mouse development: three days before birth and one, seven, 16 and 30 days after birth. Mice reach maturity a month after birth. He looked specifically at a region of the brain called the hippocampus, which is known to play a key role in learning and memory. A total of 4,390 genes showed changes in their level of activity in the hippocampus during at least one of the five time points.

Tsien used computer software to look for patterns in the gene activity and to categorize the genes according to those patterns. The computer found that the genes fit into 16 unique categories. There were 205, for example, that were very active at the first time point and then declined gradually; another 170 had the opposite pattern. Tsien noted that some of the categories fit well with the previously known functions of genes in those categories. For example, genes involved in cell division were involved in the declining group (once the animal is grown, cell division slows drastically), while those involved in regulating synapses (brain cell connections) were in the group whose activity rose during development.

"Some patterns are quite obvious; some are quite intriguing," said Tsien. "The object is to give an unbiased approach to seeing what genes are expressed and when." The information is available to other researchers through a database published at this Web site .

Contact: Marilyn Marks (609) 258-3601