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‘Inhibitory neurons are crucial for good development’

Neuroscientist Christiaan Levelt is fascinated by inhibitory neurons. ‘They used to be ignored; scientists only focused on their excitatory counterparts. But inhibitory neurons are vital for brain development.’ They play a crucial part at the start and end of critical periods, which are the ‘now or never’ stages during which, for instance, you learn to talk, or see well.

‘Inhibitory neurons play a crucial part at the start and end of the ‘now or never’ stages of development’

Levelt’s group concentrates on the visual cortex, the part of the brain that controls our sight. Brain functions such as seeing or hearing are fully developed around the eighth year of life. ‘During that critical period, the growth and withdrawal of axons is much more extensive than in the adult brain. Also, the brain forms and loses more synapses during this period. It is during this critical period that the connections between brain cells are formed and optimized. At a later age, this is a rare occurrence,’ says Levelt. ‘And that makes sense, as the connecting roads have already been laid by then.’

However, this road network is not made of concrete. It has a certain ‘plasticity’, an ability to learn. This was what Levelt discovered when he taped one eye shut in adult mice and noticed that, after a while, their visual cortex responded better to the open eye when the other eye was closed. ‘We noticed that many synapses of inhibitory neurons disappeared. And scientists who do research in other brain regions have found that plasticity increases when inhibitory neurons become less active.’

There are dozens of kinds of inhibitory neurons. The question is what exactly it is that they do. Levelt is trying to answer that question with the help of modern techniques, such as optogenetics, in vivo two-photon-microscopy and calcium imaging. ‘For about the past three years, it has been possible, through a combination of these techniques, to disentangle networks and see how they work. The strength of our lab is that we have all the tools to analyze what happens, from the molecule up to the entire system.’ He laughs. ‘I have never enjoyed my research more.’

Levelt hopes his search will bring him two things. ‘I want to understand the circuit: how do inhibitory neurons switch learning processes on or off. And I would like to know what actions will restore the plasticity in an adult system that has become dysfunctional due to a developmental disorder or a neurodegenerative disease. We will be working on that in the next few years, and I am very excited by that.’

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