Neurogenesis In The Adult

As if the processes for establishing and maintaining long-term memory weren't already complicated enough, recent findings indicate that hitherto unanticipated mechanisms also may play a role. Specifically, neurogenesis has entered the picture. When I was a young scientific sprout, the dogma was that there is no new generation of neurons in the adult CNS. However, fascinating recent results have shown that neurogenesis does indeed continue into the adult, particularly in the dentate gyrus. One key publication by Fred Gage and his colloborators showed specifically that new neurons are generated in the adult human brain (73). How might one be able to ascertain this fact? Cancer patients sometimes receive treatment with the drug Bromo-deoxy Uridine (BrdU). It selectively affects dividing cells by being incorporated into their DNA upon de novo DNA synthesis. Therefore, an ancillary aspect of this is that BrdU selectively labels freshly divided cells. Post-mortem analysis of the brains of cancer patients that had received BrdU as a chemotherapeutic treatment revealed that indeed new dentate granule cells are produced in an ongoing fashion in the adult human brain.

Are these newly generated cells important for memory? Recent work by Tracy Shors, Elizabeth Gould, and their collaborators has indicated that these new cells are necessary for memory formation, in rodents at a minimum. They have shown that both Morris water maze training and trace eye-blink conditioning lead to enhanced neurogenesis in rats (see reference 74 and figure). Moreover, inhibiting neurogenesis attenuates memory formation in these same paradigms. This fascinating paradigm shift, while at an early stage, promises to change fundamentally the types of options we need to consider when formulating models for long-term memory.

BOX 2 Learning that requires the hippocampus, but not other types of learning or a similar experience in the absence of overt learning, increases the numbers of adult-generated hippocampal granule neurons in the dentate gyrus. (A) Acquisition of the trace eye-blink conditioned response (trace paired) and the unpaired condition (trace unpaired). (B) Total numbers of BrdU-labeled cells in the dentate gyrus of these animals following trace conditioning (trace paired). These animals received BrdU injections 1 week before training and were perfused 24 hours after the last day of training. Bars represent mean ± standard error (n = 6). *significant difference (p < .01) from other groups. Continued

BOX 2 Learning that requires the hippocampus, but not other types of learning or a similar experience in the absence of overt learning, increases the numbers of adult-generated hippocampal granule neurons in the dentate gyrus. (A) Acquisition of the trace eye-blink conditioned response (trace paired) and the unpaired condition (trace unpaired). (B) Total numbers of BrdU-labeled cells in the dentate gyrus of these animals following trace conditioning (trace paired). These animals received BrdU injections 1 week before training and were perfused 24 hours after the last day of training. Bars represent mean ± standard error (n = 6). *significant difference (p < .01) from other groups. Continued

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