How the brain morphs from a cluster of cells in the womb to a fully-fledged, immensely complex organ is a huge question to answer. Breaking research uncovers the importance of early visual experience in shaping the way in which neurons behave.

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The developing brain is still shrouded in mystery.

The nature-nurture debate formed the backbone of scientific inquiry for many years.

As researchers have discovered more about the ways in which animals develop, it has become increasingly clear that both nature and nurture have vital roles.

It is no longer a discussion of whether genes or environment are the primary influence; it is now a case of understanding how each works together to create the final product. Both are equally important in their own right.

Recent research, carried out at The Scripps Research Institute (TSRI), CA, adds new information to consider. The findings help us understand how neurons in the early brain differentiate into the cell types we see in adults.

In the brain, circuits are controlled by opposing groups of excitatory and inhibitory neurons. As the names suggest, the former group tend to excite pathways whereas the latter tend to inhibit and prevent activity.

These two groups are perfectly balanced; if either set were to become dominant, the brain would either be overexcited or over-inhibited, and normal functioning would be affected.

In the developing brain, these neurons have not yet “chosen” to become inhibitory or excitatory; they are essentially identical cells in the early stages of development. How these cells make their decision to change to either excitatory or inhibitory is not yet understood.

The TSRI researchers – headed up by senior author Hollis Cline, chair of the Department of Molecular and Cellular Neuroscience and director of the Dorris Neuroscience Center at TSRI – decided to study early inhibitory neurons in tadpoles to investigate the factors that might influence the way in which they develop.

Tadpoles were chosen as the experimental animal because they are translucent, allowing their neurons to be easily observed. Also, their stages of neural development correspond to mammalian development before birth.

The tadpoles were allowed to swim freely underneath a panel of shifting lights, designed to replicate what they would see when swimming in the wild. A technique called time-lapse imaging tracked individual inhibitory neurons as they developed over time.

The results showed that, despite looking identical, the inhibitory neurons split into two opposite factions. Half strengthened their connections and increased their firing rates in response to light, in a similar way that excitatory neurons respond. A second population of inhibitory neurons decreased their number of connections and fired less in response to light.

In other words, two sets of neurons that appeared to be essentially the same responded in polar opposite ways in response to light stimuli.

One of the senior authors, and TSRI Senior Research Associate, Hai-yan He, says: “The big surprise was that neurons that look very similar have opposite plasticity responses to experience.”

The team concluded that the visual stimuli might be triggering the expression of certain genes that switch the neurons to change their type. These findings came as a “huge shock” to the researchers, who did not expect experience to make such profound changes so early in brain development.

The function of inhibitory neurons in developing circuits is defined at earlier stages of development than previously thought – and it’s defined, at least partly, by the responses of the neurons to sensory input.”

Hollis Cline

Having two subsets of inhibitory neurons poses an interesting question: how do these populations work together to keep excitatory neurons in check? Cline and her colleagues believe that one group of inhibitory neurons inhibits the other. It may work as a secondary layer of control to keep things in check.

Research into excitatory/inhibitory neuron development has the potential to be important in the design of future drugs. If a drug is being created to boost inhibitory neurons and boosts both subsets equally, it could throw the system further out of sync.

As He says: “If you target a therapy at the whole population, and disregard the diversity within that population, then you’re not actually going to achieve the intended outcome.”

Further study will be necessary to understand how these neurons change and the roles that they play, but it presents a fascinating insight into the early brain and how its amazingly complicated wiring steadily develops.

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