Windows of plasticity in brain development: What’s a neuron gotta do to open one?

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Why is it harder to learn languages when you’re older? Why do star athletes and master musicians start training young? Why are certain medical conditions reversible in kids, but not in adults?

The answer to all of these questions and many more lies in the existence of ‘critical periods’—windows of time in human and animal development when environmental experience molds neural circuits. While experience can influence the brain long before and after critical periods, the sculpting power of its hand is never quite as strong than as during these periods of heightened plasticity.

Years of research from neuroscience laboratories worldwide, including the team of Takao Hensch, director of the Conte Center at Harvard, focused on developmental origins of mental illness, has revealed that inhibitory neural activity—in which neurons release chemical signals that dampen or silence the electrical activities of their partners—plays a crucial role in orchestrating critical periods. If inhibitory neurons in the cerebral cortex don’t mature, critical periods don’t open. Conversely, if levels of inhibition are amped up early in development, critical periods can open prematurely.

But why? How exactly does inhibition allow a neuron to “open” a window of plasticity?

In a Viewpoint article published October 2^nd in Neuron, Taro Toyoizumi and colleagues, led by Hensch and Kenneth Miller of Columbia University, propose a theory: inhibition is important because it suppresses the internally driven activities of neurons and lets environmental experience have a more pronounced impact on their behavior.

You see, neural activity comes in two flavors. There’s the “spontaneous” kind that occurs regardless of what’s going on outside your body—just naturally occurring blips and dips in the electrical activities of neurons at rest. And then there’s the “evoked” kind that occurs in response to external stimuli—for instance, in the visual cortex, what happens when you see something.

The authors of this study, conducted primarily in the RIKEN Brain Science Institute in Japan, took a look at a critical period in the visual system of mice, for a form of plasticity known as ocular dominance. If you keep one eye of a mouse shut during the critical period for ocular dominance, and later examine its vision, you’ll find that there’s a clear loss of acuity in the deprived eye and substantially increased responsiveness to visual inputs from the other eye. But before or after the critical period, shutting one eye doesn’t have this effect.

The team reasoned that during this critical period—where the influence of one eye becomes stronger than that of the other—evoked activity might be playing a greater role than spontaneous activity because the spontaneous activity of visual cortex neurons is the same for both open and shut eyes, while visually-evoked activity would be higher for an open eye. So perhaps the ratio of spontaneous to evoked activity is what’s important for triggering ocular dominance plasticity.

To test this theory, the researchers developed a mathematical model centered on the workings of a single neuron in the visual cortex. Using computer simulations they used the model to describe what happens before versus during the critical period for ocular dominance, and noted that suppressing spontaneous activity and amplifying the impact of visually-driven activity produced simulated data consistent with observations from biological studies conducted in the past.

They then did the reverse experiment and looked to see if a prediction from the mathematical model holds true in a biological study. Recording the brain activities of mice exposed to flashes of LED light while in various states of ocular dominance plasticity (pre-critical period, post-critical period, and ‘open’ critical period), the researchers observed that indeed the ratio of spontaneous to evoked activity was lower when the critical period was open.

These results add credence to the general idea that our brains start to develop based on innate activity and molecular cues, but then the influence of the external world kicks in a little later, fine tuning our neural circuits in response to environmental experience. They also suggest a potential physiological basis for understanding how internal and external realities may be confounded in mental disorders. Could, for instance, the voices that some people with schizophrenia hear be due to an imbalance in spontaneous versus sound-driven activity in the auditory cortex?

There is evidence of inhibitory neuron abnormalities in schizophrenia and other neurodevelopmental disorders, and one of the hypotheses of the underlying pathology is a disruption in the cascades of critical periods that characterize normal brain development.

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For more information:

A Theory of the Transition to Critical Period Plasticity: Inhibition Selectively Suppresses Spontaneous Activity
Full text of the scientific article in Neuron

New theory on how inhibitory brain activity ‘turns on’ critical periods
Conte News brief on Neuron article