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The Widening Gyrus

Concert pianists could be model organisms for studying the physiological basis of intellectual greatness

Charles T. Ambrose

Plasticity in the Adult Brain

The dogma of neurophysiology up until the 1970s was that generation of new neurons was limited to the period of embryogenesis for most of the brain, with a few exceptions, including the granule cells of the olfactory bulb and hippocampus. After birth, regeneration of neurons was believed to be limited to the peripheral nerves. As it became clear that all cortical areas of the brain exhibit plasticity (changes over time), modulations in function and activity were ascribed to synaptic changes. However, recent studies have suggested that neurogenesis may also be in play. Following are nine reports that describe simple enlargement of the brain or an increase in the volume of specific cortical areas after various stimuli. In the first four reports neurogenesis was not considered by the researchers; in the latter five reports, it plainly occurred.

In the early 1980s, William Greenough and colleagues trained adult rats on multiple maze patterns and found that afterward, “visual cortex pyramidal neuron dendritic fields were larger” than in controls. Rats trained on complex motor tasks also showed greater “cerebellar cortex thickness” than control rats given “far more physical activity” using devices such as treadmills. According to the authors, the results “strongly implicate changes in the number of synapses in the memory process.” They did not pursue a conclusive histological investigation.

In the 1990s, Gregg Recanzone and coworkers trained monkeys “to discriminate between two vibrating stimuli applied to one finger” and after several thousand trials found that “the cortical representation of the trained finger became more than twice as large as the corresponding areas for other fingers.”

In 1995, Thomas Elbert used neuroimaging to study right-handed string musicians and found that “the cortical representation of the fingers of the left hand … was larger than that in controls.”

2010-07MacroAmbroseFC.jpgClick to Enlarge ImageIn 2004, Bogdon Draganski and colleagues employed fMRI scans of young volunteers who had mastered over a three-month period “a classic three-ball cascade juggling routine” and found expansion in gray matter in the mid temporal area and left posterior intraparietal sulcus. Notably, the expansion decreased three months later.

In the following five reports, postnatal neurogenesis was explicitly addressed.

Studies by Fernando Nottebohn in birds may have relevance to neurogenesis in the human brain. In the early 1980s, Nottebohn’s lab reported in several papers that in the female canary forebrain (hyperstriatum), the volume of two vocal control nuclei (functional collections of neurons and associated cells) increased markedly during the peak of the singing season, then declined, then increased again during the successive singing season. The song repertoire of the canaries changes each year. The birds were injected with 3H-thymidine, which becomes incorporated in the DNA of replicating cells. In birds that received the label, it was shown that the volume increase in one particular area was accompanied by labeled glial, endothelial and migrating neuronal precursor cells—all of which were interpreted as signs of neurogenesis.

The earliest neurological studies using radioactive labeling were done in 1962 by Joseph Altman, who injected 3H-thymidine into lesions created in the lateral geniculate body of adult rats. He found labeled glial cells, neuroblasts, and a few neurons in or near the lesion area. The presence of labeled neuroblasts was judged to support “a process of neurogenesis” in the area of repair.

In 1999, Elizabeth Gould and coworkers injected bromodeoxyuridine (BrdU, a synthetic nucleotide analog that, like 3H-thymidine, gets incorporated into DNA in replicating cells) into adult macaques and after one week found labeled mature neurons in the prefrontal, inferior temporal and parietal cortices, indicating that neurons “are added to primate neocortex in adulthood.” The authors did not regard the prior studies by Altman and Nottebohn as definitive or as establishing neurogenesis.

Peter Ericksson and colleagues reported in 1998 on the injection of five terminally ill patients with BrdU. They found that after their deaths (from several weeks to two years later), cells in the hippocampal dentate gyrus were labeled with both BrdU and a neuron-specific marker. They interpreted their findings to indicate the “genesis” of new neurons from “dividing progenitor cells” in the gyrus.

Finally, work by Marian Diamond and colleagues indicated that the continued growth of human brain after birth is influenced by nutritional factors and environmental influences. They found that rats given playthings and treadmills (“an enriched environment”) develop more glial cells per neuron in the occipital cortex. Other changes noted were “neuronal stroma size, neuronal density, length of dendritic branches, dendritic spine density, length of synapses and glial cell counts.”

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