One of the grand strategies nature uses to construct nervous systems is to overproduce neural elements, such as neurons, axons and synapses, and then prune the excess. In fact, this overproduction is so substantial that only about half of the neurons mammalian embryos generate will survive until birth.

Why do some neural connections persist, whereas others do not? A common misconception is that neurons that do not make the cut are defective. Although some may indeed be damaged, most simply fail to connect to their chemically defined targets. In a series of brilliant studies performed during the latter half of the 20th century, researchers discovered how pruning works. They found that newborn neurons migrate along chemically defined routes and that when the neurons arrive at their genetically assigned locations, they compete with their “sibling” neurons to connect with predetermined targets.

Victorious neurons receive trophic, or nourishing, factors that allow their survival; unsuccessful neurons fade away in a process called apoptosis, or cell death. The timing of cell death is genetically programmed and occurs at different points in the embryonic development of each species.

For decades neuroscientists believed that neural pruning ended shortly after birth. But in 1979 the late Peter Huttenlocher, a neurologist at the University of Chicago, demonstrated that this excess production and pruning strategy actually continues for synapses long after birth. Using electron microscopy to analyze carefully selected autopsied human brains, he showed that synapses—the tiny connections between neurons—proliferate after birth, reaching twice their neonatal levels by mid- to late childhood, and then decrease precipitously during adolescence.

These changes at the synapse level cause neural restructuring that very likely has important consequences for normal and abnormal brain function. Streamlining neural circuits could explain the boost in cognitive skills that occurs in our late teens or early 20s. The loss of redundant pathways could help elucidate why we have difficulty recovering from a traumatic brain injury: eliminating synaptic redundancies diminishes our ability to develop alternative pathways to bypass the damaged region.

In addition, many major mental illnesses start to emerge in adolescence, which may be caused by aberrant synaptic pruning. In 1982 I hypothesized that disordered synaptic pruning could explain the age of onset of schizophrenia, and in 2016 researchers published genetic and experimental evidence supporting this association in Nature.

Although we are only beginning to unravel the ramifications of synaptic pruning in the human brain, this process clearly has significant consequences for normal human brain function and may provide key insights into the causes of some devastating and mysterious neuropsychiatric diseases.

Question submitted by Rowena Kong via e-mail.

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