Try the training regimen of an Olympic athlete for a few days and two things will likely happen: you will be physically unable to complete the tasks and it will hurt, a lot. That’s because, as you overexert your muscles, they will tell your brain that it’s simply not possible to do what you want them to do and that, if you keep doing it, you will be in pain. There is no alternative path between your muscle cells and nerve cells that could send your brain a different message. But that wasn’t always the case. At the very beginning of life, our brains contain many possible connections between neurons and connecting cells.
New research conducted by scientists in the lab of Jeff Lichtman at Harvard’s Department of Molecular and Cellular Biology used light microscopy and a new technique called serial electron microscopy to show that, right before mice are born, muscle cells connect to up to ten different nerve cells . A few days after birth, the body and brain determine which of the neuron branches, or axons, will connect permanently and which will be terminated. This research indicates that we are born with at least ten different potential connection pathways between any given muscle in the body and the brain, and only one survives.
Powerful imaging technologies
For decades, the prevailing philosophy of brain development has been that neurons make multiple connections during an organism’s early postnatal growth, and these connections are subsequently pruned away as some become more useful or relevant than others. However, Lichtman’s innovative use of imaging technology, genetic engineering with fluorescent protein molecules to illuminate connectivity between cells, and his decision to observe mice before the typical 7-days old mark, have now allowed scientists to see the type and quantity of individual connections that are made just before and after birth.
Lichtman’s team used serial electron microscopy, a relatively new tool. It was invented in 2004 as a way to capture three-dimensional and high-resolution images and has been primarily used in the field of neuroscience. It functions exactly like an optical microscope except that it uses a beam of electrons (negatively-charged subatomic particles) rather than a light beam, and it measures the interactions between the electrons and the sample to produce an image. Electron microscopy, which is able to image samples at the nanometer-level (1 billionth of a meter, or 1000 times more powerful than traditional imaging techniques), is especially effective in imaging neurons and neuron interactions since their connections, or synapses, are exceptionally small. In this way, serial electron microscopy is able to capture images of the axons and synapses of neurons by detecting the electrons that reflect off of the stained surface of a given sample.
Serial electron microscopy images from Lichtman’s team indicate that the number of connections between nerve cell axons and muscle cells actually decreases by 90% from birth to adulthood. Additionally, it is not only a difference in quantity ― at birth the connections are complex and diffuse, but after birth, those connections become more concentrated. The axon terminal branches prune back, or die off, leaving one axon to remain, elongate, thicken and strengthen its connection with the receiving cell. This axon then serves as the lone communication channel between its one corresponding muscle cell and the brain for the rest of the organism’s lifetime.
With these imaging results, scientists have evidence that the number and diversity of connections made between axons peaks at birth. Whether or not those connections persist later in life is largely influenced by the environment. As Lichtman says, “Rather than allowing our genes to tyrannize our behavior, we more than any other animal are under the tyranny of the environment we find ourselves in.” Lichtman hopes that this understanding, in addition to the technologies that are enabling scientists to see increasingly tiny units earlier and earlier in development, may be able to improve our understanding of behavior and learning disorders. It also adds to the growing body of literature, based primarily on neuroimaging techniques, on synaptic connections during early childhood development, much of which highlights the impact of physical learning and social environments on an individual’s development.
Neurological development in humans
One of the most widely used brain imaging techniques is called fMRI (functional magnetic resonance imaging), which uses a giant rotating magnet to measure signals correlated with brain activity. Studies using fMRI technology have shown that many of the connections that make humans uniquely humans, namely those in the prefrontal cortex (the very front part of the brain and the last part to form mature synaptic connections), continue to prune and strengthen over the course of adolescence and into early adulthood.
These studies of interactions between neurons are important because they help scientists understand the connections that enable humans to focus their attention and make deliberate decisions, attributes that we often reward in social and academic settings. While serial electron microscopy and fMRI measure different kinds of connections, they indicate a similar phenomenon; just as there are an infinite number of possible connections between nerves and muscle cells during early development in all mammals, there is also an infinite number of possible outcomes during this later and uniquely human phase of development. Humans, in short, become who they are slowly, over time, and in a process that is highly influenced by their environment.
Why is the development of the human brain so easily influenced by the environment? There is strong evolutionary reasoning behind this deliberate developmental trajectory and it is part of a larger hypothesis for why humans have become such a dominant and persistent species. Having brains that develop their most important connections over a long timeframe may have allowed humans to adapt to a wide variety of global environments, enabling our ancestors to migrate and settle throughout the planet. Today, humans inhabit a diverse number of physical, social and virtual environments. Our highly adaptable neurological development gives each new generation the ability to innovate and create within these continuously changing worlds.
Jessica Ellis is an alumna of the Mind, Brain and Education program at the Harvard Graduate School of Education.
 Tapia, J., Wylie, J., Kasthuri, N., Hayworth, K.J., Schalek, R., et al. (2012). Pervasive synaptic branch removal in the mammalian neuromuscular system at birth. Neuron, 74: 816–829.
 Reuell, Peter. The Growing Brain. Harvard Science, June 25, 2012. http://news.harvard.edu/gazette/story/2012/06/the-growing-brain/
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