New Cells Thrive in Brain's Learning Center

1. T.J. Shors et al., "Neurogenesis in the adult is involved in the formation of trace memories," Nature, 410:372-5, March 2001. For this article, Leslie Pray interviewed Tracey Shors, behavioral neuroscientist and associate professor in the psychology department at Rutgers University. Data from the Web of Science (ISI, Philadelphia) show that Hot Papers are cited 50 to 100 times more often than the average paper of the same type and age. E. Gould, A. Beylin, P. Tanapat, A. Reeves, T.J. Shors, "Learning enhances adult neurogenesis in the hippocampal formation," Nature Neuroscience, 2[3]:260-5, March 1999. (Cited in 132 papers) Courtesy of Tracey Shors Tracey Shors For decades, biologists believed that brain cells didn't regenerate. But over the past several years, researchers from a handful of laboratories across the country, including Elizabeth Gould's lab at Princeton University, proved this opinion to be wrong. Indeed, up to 5,000 new cells are generated in the hippocampus every day, says Tracey Shors, behavioral neuroscientist and associate professor at Rutgers University, and a coauthor on this Hot Paper. The hippocampus, or hippocampal formation, is a region of the mammalian forebrain involved with memory and learning. For Shors and Gould, it was a logical next step to ask whether this new cell growth in the hippocampus was connected with hippocampus-dependent learning. What they discovered was both expected and surprising: Since the hippocampus is the neurological seat of learning, it made sense that the new cell growth was affected, but researchers didn't expect the evidence to be so strong. Tasks and Tests Shors, Gould, and their collaborators set up behavioral tasks to test the effect of hippocampal-dependent learning on new-neuron generation in an area of the hippocampal formation known as the dentate gyrus. In one test called the Morris water maze, researchers trained rats to use various spatial cues to find a transparent platform in a pool of water. When the platform is submerged, the animals need their hippocampus so they can learn the cues to find it. But there is also a hippocampal-independent way to train animals: learning how to find the platform when it's above the surface is simpler and doesn't require the hippocampus. Shors and her collaborators compared the results of the two different types of training to see how they affected neurogenesis. In a second test, the researchers used what's known as classical eyeblink conditioning to elicit a basic Pavlovian response: the animals hear a tone and then receive stimulation that makes them blink their eyes. This happens repeatedly until the animals learn that the two stimuli are associated and blink when they hear the tone. As with water-maze training, two ways exist to train the animals. One involves the hippocampus, the other does not. Again, researchers compared how the two modes of learning affected new neuronal growth. Prior to carrying out the tests, researchers injected the animals with a stain (BrdU) that only newly generated cells would absorb. After the tests, the number of BrdU-labeled cells were counted and used as a measure of neurogenesis. In both tests, the researchers found that hippocampus-dependent conditioning increased the survival of newly generated neurons, whereas hippocampal-independent conditioning did not. Discoveries and New Questions The researchers found that compared to untrained controls, the number of new neurons that survived were double in rats that had been trained on hippocampus- dependent tasks, but remained the same in animals trained in a hippocampus- independent manner. "In reality, the learning did not generate new cells but rather enhanced the survival of cells that were generated prior to learning," Shors says. Of the thousands of new cells that are generated in the hippocampus daily, "the vast majority die within weeks," says Shors. "But there's something about hippocampus-dependent learning that rescues them from death." While their results weren't unanticipated, says Shors, it was "certainly surprising to obtain such a clear answer. I don't think either of us expected that learning would have such a unique effect on these cells, that the effect would be so specific to hippocampal-dependent learning." This study "changes our perspective on how plastic the hippocampus is," explains Shors, but it doesn't clarify what the cells are actually doing. The two women, says Shors, are still trying to find out what role these cells play in hippocampus-dependent learning. In a follow-up study that appeared in Nature this past March,1 the researchers conducted similar conditioning experiments and showed how a reduction in the generation of new neurons in the hippocampus impairs hippocampal-dependent learning. So not only does hippocampal-dependent learning affect the new cells, but the new cells affect learning. They still don't know what the cells are actually doing, but at least, says Shors, this "gets us one step closer." Leslie Pray (lpray@nasw.org) is a freelance writer in Leverett, Mass.

New Cells Thrive in Brain's Learning Center

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