Until recent decades, the brain was viewed as static. The accepted scientific view was that after early childhood few changes occurred in the connections between neurons and no new brain cells appeared. A new, dynamic model of the brain has emerged from this fixed model. This transition was marked, first by scientific acceptance of the ability of existing neurons to change (neuroplasticity), and then in 1998, of neurogenesis, the formation of new adult brain cells in humans. A series of studies revealed that changes such as the rapid growth of new nerve fibers and connections between them occur on a daily basis. We now know that if new synapses (junctions between nerve cells) are not used, they are rapidly pruned. New research details increasingly complex ways that neurons change. For example, the memory for coordination of movements includes various changes in multiple brain regions--including the brain's cerebral cortex, or outer covering, the hippocampus, a region critical for memory, and the cerebellum, the hub for motor coordination. [caption id="attachment_41" align="alignleft" width="250" caption="Scientists are finding brain cell growth in various regions of the adult and adolescent brain. Image: iStock/Jana Bla?kov?"][/caption] As exciting as these developments have been in revealing the capacity of the brain to adapt, change, and grow, even more exciting has been the discovery of new cells minted from neural stem cells in the adult human brain. Early enthusiasm about the possibility of new neurons in many parts of the brain was eventually tempered by the realization that only two regions of the brain appeared to actively make new cells--the major centers for memory and smell. Recently, it has become very clear that, in the hippocampus, these new cells are a critical part of the day-to-day memory process. So, it is very surprising, and perhaps encouraging, that a research group at Michigan State University has found in hamsters what appear to be new cells in the amygdala, which governs fear and other feelings, as well as in connected regions of the limbic, or emotional, brain system. Also surprising is that these new cells were found in the adolescent brain. This report appears in the Proceedings of the National Academy of Sciences, March 4, 2013. Prior to this paper, no one has revealed finding new cells in any limbic region. If this study is validated, scientists may eventually discover that other parts of the brain also produce new cells. Birth of Neurons in the Fetus New brain cells are created at a fantastic rate during fetal development. In the last month of pregnancy, new neurons appear and migrate to appropriate places at the rate of 250,000 new neurons per second, resulting in almost a trillion cells at birth. These neurons are then rapidly pruned to the 80 to 100 billion that we maintain throughout life. This pruning of neurons is a clean, orchestrated destruction of cells that occurs without inflammation. After the fetal period, only a relatively small number of brain cells are made each day and only in the centers for memory and smell--and possibly, now, in the amygdala. Adult Neurogenesis Since the first discovery of neurogenesis in adults, researchers have looked for new neurons in various brain regions. An early study confirmed that new cells are formed in the hippocampus, specifically in the sub-granular zone of the dentate nucleus. Later, they were observed in the olfactory bulb, with thousands of them reaching the olfactory bulb each day. These neurons originate in the sub-ventricular zone, and then migrate in the rostral migratory stream. These new cells correlate with olfactory learning and memory. There is an increasing understanding of the importance of new hippocampal cells to daily functioning. Recent work has shown that not only do these cells reflect new learning, but they are also more plastic than older hippocampal cells, have more widespread connections, and underlie the learning of especially difficult cognitive tasks. These new memory cells respond to new information, not to old memories. They also have a distinct function, that of "pattern separation:" they form memories based on specific differences, such as that between two cars. Existing neurons, on the other hand, are used for "pattern completion:" memories based on similarities such as which of the cars a friend was driving. New cells in the hippocampus also play a prominent role in the treatment of depression. Antidepressants, psychotherapy and changes in lifestyle all stimulate the important brain-derived neurotropic factor, BDNF, which promotes the creation of new cells. Other events that appear to stimulate BDNF and new cell growth are physical exercise and "enriched environments." Factors that lower BDNF and block new cell growth, thus affecting memory, include depression, lack of sleep, chronic stress and aging. Interestingly, gut microbes influence BDNF through unknown blood signals, possibly involved in the development of depression. In addition, HIV appears to cause dementia through a complex mechanism involving BDNF. Once in the brain, the virus' surface protein latches onto the BDNF precursor, pro-BDNF, stopping production of new brain cells. The creation of new brain cells can also have negative effects. Addiction, for example, is a learned behavior that uses new brain cells and new neuronal connections. A very intriguing study in mice showed that exercise creates a window of opportunity for new memory cells, and those mice given cocaine in the hours after physical training developed stronger addictions. Adolescent Cells Previous efforts to discover new brain cell formation have focused on infants and adults. Prior to 2013, it was not widely considered that adolescence might be a time of new cell development, although in retrospect it would be logical to consider that it might. Adolescence and the onset of puberty is a time of tumultuous growth and change, including new social learning and the new pressures of mating. This period of dramatic change seems a propitious time to have increased cells for learning and memory, especially emotional and social learning. [caption id="attachment_43" align="alignright" width="268" caption="Social learning during adolescence may partly reflect the birth of new neurons. Image: iStock/Skip ODonnel"][/caption] It has now been shown that extensive brain remodeling occurs in adolescence, including some neurogenesis. One recent study at Yale showed that blocking production of new cells in adolescent mice made them very antisocial, whereas the same interruption in adults did not. Although normal mice spend considerable time interacting and exploring, without the production of new cells in adolescence, they lacked interest in social activities--it appeared as if they didn't even recognize other mice. This observation implies that neurogenesis is critical to social life in adolescence. The authors of this study assumed the new cell production was in the hippocampus; they did not consider the possibility that it was in the amygdala. In the recent study in adolescent hamsters, however, the Michigan State team discovered new cells in the amygdala and connected limbic regions--areas in which such cells had never been seen. These limbic regions are related to social learning, evaluation of facial expressions and body language, and are very important for mating behavior. The Michigan scientists noted that these new cells were not minted and then promptly destroyed, as happens to many cells, but were fully integrated into the brain circuitry. It is extremely difficult, involving painstaking work, to find a few small cells in the brain. But, new brain cells, either stimulated to grow from existing neural stem cells or added as stem cell treatments, are the holy grail of neuroscience because they allow the development of new brain structures or renewal of older structures. If these results in the amygdala and the limbic system hold up, they will rekindle the excitement from the days when researchers first recognized neurogenesis. The finding begs an intriguing question: Could there be an orchestration of other new brain cells in different critical regions, carefully timed for important milestones in human development?
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