November 29, 2010
Of Mice and Memory
Years ago, London neurobiologists discovered a way to visualize the structural dynamics of memory formation using just a laser, a microscope, and a window. To start, they vivisected the craniums of dozens of laboratory mice and surgically embedded tiny glass panels into the outer fleshy folds of the living, exposed brains.
The researchers specifically targeted an area of the brain known as the visual cortex; their goal was to define the relationship between vision and memory. These implanted bits of glass were to serve as physical windows to the branching, ductile neurons of the brain; when scanned by a laser, they would allow for capture of microscopic images of fluorescing neurons and provide a glimpse into the creation of memories.
In 2009, their laborious efforts paid off. Mark Hubener’s lab at University College reported in January’s issue of Nature magazine that they had found a link between distinct neural growths and memories of past experiences. Through miniscule peepholes, Hubener’s team saw bud-like spines emerging from the branches of the brain’s neurons. These spines seemed to sprout most in response to new experiences, implicating them as the brain’s physical storage areas for memory.
Because Hubener’s work is fairly visual in nature, it’s easiest to begin with a mental picture of the brain. Let’s start by imagining its most basic component, the neuron, as a tree in winter, leafless with many branches, or dendrites. If the neuron is a tree, then the brain, quite simply, would be the forest where it resides. Now, if you can imagine that forest with one hundred billion trees densely packed into a space the size of a grapefruit, then you’ve got a basic idea of what the human brain looks like.
Not impressed? Each tree in your brain forest physically contacts the branches of thousands of other trees; in children, these contacts, or synapses, number a quadrillion, in adults, this number decreases then stabilizes to a mere few hundred trillion. If synapses were dollars, we’d have enough money to pay for the Bush administration’s tax cuts... for two thousand years*.
So, what’s the purpose of all of these branching contacts? Synapses serve as conduits of communication between neurons- they allow information to race from dendritic branch to dendritic branch, relaying messages of sense, perception, reaction, and thought. But what about memory? Where are our recollections of past experiences stored among this vast network of neurons?
Much of what we know about experience-based memory comes from research in laboratory animals. In particular, a technique called monocular deprivation (MD) has been widely used to learn about the dynamic neural connections that link the eye with the brain. This technique, as the name suggests, involves blocking vision in one eye of an animal (picture a mouse with an eye-patch), and monitoring brain activity as the animal adapts to its new uni-vision.
Other than faint light perception, all stimulation through the covered eye is lost, silencing the once rapid conversation between eye and brain. After just a few days of deprivation, however, the brain acclimatizes and abandons the non-communicative neural branches of the sightless eye for those of the uncovered, seeing eye.
Why is this sensory deprivation technique useful? Forcing the brain to adapt to new experiences offers clues into memory formation. As we’ve learned from mice, once the eye-patch is removed, adult animals fully recover binocular vision, as if they’d never been blinded. However, if the eye is covered a second time, the brain seems to remember how it dealt with one-eyed vision in the past, and accelerates the shift in dominance to the uncovered eye. The easy return to standard two-eyed vision after MD belies lasting changes made in the animal’s neural architecture.
While it is relatively simple for an adult animal to switch between one and two-eyed vision, covering the eye of a young animal can result in irreversible blindness, even long after the eye-patch has been removed. Why are young animals so vulnerable to changes in sight, while adults can easily adjust? Let’s revisit our brain forest, and imagine that everything has been newly planted.
As saplings, trees are pliable, and easily manipulated by outside forces. However, the fleeting events of youth have long-term consequences, and something as trifling as a pebble in the soil can forever transform the structure of a new tree.
Similarly, because neuronal branches establish their connections during infancy and childhood, minor changes in sensory input during this time period can drastically alter the structure of the developing brain. As soon as one part of a young brain stops receiving messages, neighboring neurons encroach upon the vacant territory, competing for new connections that will persist into adulthood.
If our network of neurons is essentially fixed after childhood, how are we able to adapt to new experiences as adults? Why are mature animals able to ‘learn’ how to see out of one eye? Let’s get back to Hubener’s mice. Using the tiny brain-implanted windows, Hubener’s team chronicled the ebb and flow of miniscule dendritic branch protrusions after MD to uncover their role in memory storage. These small spines budded from the branches of neurons in response to MD and persisted long after the sightless eye was uncovered.
When the same eye was covered a second time, Hubener’s team saw no new spine formation, despite swift adaptation to monocular vision. They proposed that dendritic spines carry synapses and serve as local reservoirs of memory, allowing the brain to structurally adapt to new experiences while maintaining its overall neuronal organization.
Hubener’s team peered into the mouse brain and traced the structural framework for memory through its pathways. They were the first to link experience with dendritic spine formation, and confirmed that new experiences can actually change the physical layout of the brain.
We still don’t know how long these memory spines persist- this study only followed individual mice for 2-3 weeks. It’s possible that the loss of spines is connected with memory loss, or with neurodegenerative diseases. However, we do know that practice, or repetition, allows the brain to learn and adapt more quickly to new experiences, and that spine formation is fundamental to this type of experiential memory.
*The Treasury Department estimates (roughly) that the cost of a short-term extension of the Bush era tax cuts is between $200 billion and $500 billion. This estimate depends on how long the cuts are extended, and for whom. If I use the upper end of this estimate, and say that a one-year extension will cost $500 billion, then a quadrillion dollars would pay for two thousand years of tax cuts. Alternatively, if the tax cuts cost only $200 billion per year, a quadrillion dollars would cover five thousand years of tax cuts.
1. Alberts, B. (2002). Molecular biology of the cell. New York : Garland Science.
2. Drachman, D. A. (2005). Do we have brain to spare?. Neurology, 64(12), 2004-5.
3. Dräger, U. C. (1978). Observations on monocular deprivation in mice. Journal of Neurophysiology, 41(1), 28-42.
4. Hofer, S. B., Mrsic-Flogel, T. D., Bonhoeffer, T., & Hübener, M. (2006). Lifelong learning: Ocular dominance plasticity in mouse visual cortex. Current Opinion in Neurobiology, 16(4), 451-9.
5. Hofer, S. B., Mrsic-Flogel, T. D., Bonhoeffer, T., & Hübener, M. (2009). Experience leaves a lasting structural trace in cortical circuits. Nature, 457(7227), 313-7.
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