Making up for lost time: Inhibitory neurons catch up during brain development

The human brain is made up of billions of nerve cells, or neurons, that communicate with each other in vast, interconnected networks. For the brain to function reliably, there needs to be a fine balance between two types of signals: Excitatory neurons that pass on information and increase activity, and inhibitory neurons that limit activity and prevent other neurons from becoming too active or firing out of control. This balance between excitation and inhibition is essential for a healthy, stable brain.

Inhibitory neurons are generated during brain development through the division of progenitor cells – immature cells not yet specialized but already on the path to becoming neurons. The new study, led by researchers at the Max Planck Institute for Biological Intelligence, uncovered a surprising feature of brain development based on findings in mice: During this essential process, cells born later in development mature much more quickly than those produced earlier.

“This faster growth helps later-born neurons catch up to those produced earlier, so that by the time all these neurons are incorporated into neural networks, they are at a similar stage of development,” said Christian Mayer, research group leader at the Max Planck Institute for Biological Intelligence. “This is important, as otherwise, earlier-born neurons—having had more time to form connections—could end up with far more synaptic links than those created later. Without this adjustment, the network could be thrown off balance, and individual cells would have too many or too few connections.”

In the study, the researchers also explored how the accelerated maturation of later-born inhibitory neurons is regulated. They identified specific genes involved in this process and uncovered how they control when and to what extent a cell reads and uses different parts of its genetic code. They found that the faster development of later-born inhibitory neurons turns out to be linked to changes in the developmental potential of the precursor cells that generate them—changes which are, in turn, triggered by a reorganization of the so-called ‘chromatin landscape.’ In simple terms, this means that cells adjust the accessibility of certain regions of DNA in the cell nucleus, making key instructions on how and when to develop more readable.

Genetic changes, such as mutations or altered gene regulation, in these genes or processes may alter the developmental pathways of the brain during early embryonic stages, which could contribute to the development of conditions such as autism or epilepsy. Therefore, this study could ultimately offer insights into how developmental disorders of the brain can begin so early in life.

In the study, the researchers also explored how the accelerated maturation of later-born inhibitory neurons is regulated. They identified specific genes involved in this process and uncovered how they control when and to what extent a cell reads and uses different parts of its genetic code. They found that the faster development of later-born inhibitory neurons turns out to be linked to changes in the developmental potential of the precursor cells that generate them—changes which are, in turn, triggered by a reorganization of the so-called ‘chromatin landscape.’ In simple terms, this means that cells adjust the accessibility of certain regions of DNA in the cell nucleus, making key instructions on how and when to develop more readable.

Genetic changes, such as mutations or altered gene regulation, in these genes or processes may alter the developmental pathways of the brain during early embryonic stages, which could contribute to the development of conditions such as autism or epilepsy. Therefore, this study could ultimately offer insights into how developmental disorders of the brain can begin so early in life.

The newly discovered mechanisms highlight just how important both genetic factors and the correct pace of development are for a healthy brain. They may also open up new approaches to studying the causes of neurodevelopmental disorders, and potentially one day help to inform the development of treatments.

Original publication

Ann Rose Bright*, Yana Kotlyarenko*, Florian Neuhaus*, Diana Rodrigues, Chao Feng, Christian Peters, Ilaria Vitali, Elif Dönmez, Michael H. Myoga, Elena Dvoretskova, Christian Mayer
*these authors contributed equally; Temporal control of progenitor competence shapes maturation in GABAergic neuron development in mice; Nature Neuroscience, online July 8, 2025
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