Researchers Discover New Cellular Mechanisms Involved in Visual Memory, Amblyopia


CAMBRIDGE, MASS. —Researchers led by Massachusetts Institute of Technology professor Mark Bear discovered new cellular mechanisms serving visual recognition memory, in which the brain learns what sights are familiar so it can focus on what’s new, and of a potential therapy for amblyopia, also called lazy eye. They found that both of these conditions depend on the presence of key proteins called NMDA receptors in the neurons in layer 4 of the visual cortex, an area that is thought to directly receive visual information.

Bear and his team expected to confirm that NMDA receptors act specifically in neurons in layer 4 of the visual cortex to make the circuit connection changes, or “plasticity,” necessary for both visual recognition memory and amblyopia. However, their study produced unexpected results.

“There are two stories here,” Bear, co-senior author and Picower Professor of Neuroscience in The Picower Institute for Learning and Memory, said in a summary of the research findings published on the Institute's website. “One is that we have further pinpointed where to look for the root causes of amblyopia. The other is that we have now completely blown up what we thought was happening in stimulus-selective response potentiation, or SRP, the synaptic change believed to give rise to visual recognition memory.”

The researchers explained that the cortex is built like a stack of pancakes, with distinct layers of cells serving different functions. Layer 4 is considered to be the primary “input layer” that receives relatively unprocessed information that arises from each eye. Plasticity that is restricted to one eye has been assumed to occur at this early stage of cortical processing, before the information from the two eyes becomes mixed.

Their evidence demonstrates that NMDA receptors in layer 4 neurons are indeed necessary for the degradation of vision in a deprived eye, but they apparently play no role in how neural connections, or synapses, serving the uncompromised eye strengthen to compensate, and similarly don’t matter for the development of SRP.

For the study,the researchers used a genetic technique to specifically knock out NMDA receptors in excitatory neurons in layer 4 of the visual cortex of mice. By doing this, they can investigate the consequences for visual recognition memory and “monocular deprivation,” a lab model for amblyopia in which one eye is temporarily closed early in life.

Ming-fai Fong, lead author of the study, said this new research highlights the ongoing need to identify “distinct components in the visual cortical circuit that mediate visual enhancement” which will be important in developing treatments for visual disability.

Fong said that with continued work, the lab hopes to pinpoint where in the circuit NMDA receptors are triggering SRP and the compensatory increase in strength in a non-deprived eye after monocular deprivation. Doing so, she said, could have clinical implications.

The National Eye Institute and the JPB Foundation funded the study.