The brain is not born ready to process everything the entire world might send its way. Instead, its nature is to be flexible and adaptable to experience, especially during development, but even in adulthood. This ability to “rewire” to incorporate experience is called plasticity and takes many forms. Like several other labs in the Picower Institute (see here, and here and here], the lab of Mriganka Sur, Newton Professor of Neuroscience, has made important discoveries of mechanisms of neural plasticity.

Neuroscientists now understand that plasticity becomes manifest at the connection between two neurons called a synapse and that most of the synapses neurons form to receive input from others reside on their dendrites, which are the root-like projections that sprawl outward from the cell body. Several of the Sur lab’s earlier discoveries about plasticity helped to advance this understanding by using cutting edge imaging methods in live animals to track the fate of the spines on those dendrites that house many synapses. In 2003, for example, the lab showed an important connection between plasticity and changes in spine growth by demonstrating that if they varied the visual experience of young mice during the critical period of their development (kept them in the dark vs. the light), the spines would show much distinct degrees of change. The next year they identified specific molecular processes that allow that dendritic spines to remodel quite quickly, for instance when one eye is temporarily deprived of input by being closed for a few days. During development, such “monocular deprivation” can cause the visual cortex to rewire connections serving the occluded eye to instead serve the unobstructed eye, a phenomenon called ocular dominance plasticity. In 2010 they found that synaptic changes in the visual cortex following dark-rearing and then light exposure correlated strongly with functional changes in visual development.

Plasticity is more pronounced during initial development but is a lifelong process.  In 2006 they found that while sensory areas of the brain show much greater degrees of dendritic spine change in mouse pups vs. even young adults, they reported some remodeling going on even in maturity, too.

The Sur lab has not only looked at changes among synapses on dendritic spines, but also at the underlying molecular factors that enable those changes.  In a screen or survey of molecules involved in ocular dominance plasticity carried out in 2006, they discovered a host of genes, molecules and molecular pathways that were implicated in synaptic plasticity. Remarkably, some of the molecules discovered in this screen were used to restore normal plasticity and function in animal models of brain disorders.

In a 2011 study, the lab found that when young mice were exposed to light after being reared in the dark, neurons in the visual cortex dramatically increased production of a microRNA called miR-132. Inhibiting miR-132 prevented ocular dominance plasticity in identified neurons following monocular deprivation and affected the maturation of dendritic spines, revealing a critical role for the microRNA in visual cortex plasticity.

Above: A dendrite with round processes or spines, expresses a red fluorescent protein together with a green tag for the protein Arc, obtained with two-photon microscopy.

A year earlier the lab, working with that of Picower Professor Mark Bear, also found that the protein Arc was similarly crucial for enabling plasticity. In mice lacking Arc, the visual cortex proved impervious to effects from deprivation or experience. Arc also played a central role in the Sur lab’s discovery in 2018 of a new rule of synaptic plasticity. Focusing on a visual cortex neuron whose job was to respond to locations within a mouse’s fied of view, the team purposely changed which position was preferred by manipulating a form of plasticity. That shift toward processing a different input strengthened a particular synapse on the neuron. When that happened, the team observed that nearby synapses commensurately weakened to ensure a consistent overall level of input. Arc proved essential to orchestrating that rebalancing.