Motor circuits in brain can be repaired with newly grown neurons and so reverse damage caused by Huntington’s disease

VIDEO: The study has revealed that the adult brain can generate new neurons that integrate into key motor circuits – an insight that challenges long-held beliefs about adult neurogenesis. The research, which can trace its origins to studies in canaries that generate new neurons as they learn songs, shows that stimulating the brain’s progenitor cells may repair damaged neural networks in Huntington’s disease. Credit: University of Rochester Medical Center/Del Monte Institute for Neuroscience

The adult brain has been shown to generate new neurons that integrate into key motor circuits – recent research has shown – demonstrating that stimulation of natural brain processes can help to repair damaged neural networks in Huntington’s and other diseases.

It has been conventional wisdom that an adult brain cannot generate new neurons. However, there is now growing understanding that certain portions of the brain have reservoirs of progenitor cells which are able of producing neurons.

These cells actively produce neurons during early development of the brain but at birth switch over to produce glia support cells. One of the areas of the brain where these cells are found is the ventricular zone – next to the striatum – a part of the brain severely affected by Huntington’s.

“Our research has shown that we can encourage the brain’s own cells to grow new neurons that join in naturally with the circuits controlling movement,” said Dr. Abdellatif Benraiss, a senior author of the study, and research associate professor in the University of Rochester Medical Center (URMC) lab, in the United States.

“This discovery offers a potential way to restore brain function and slow the progression of these diseases,” he added.

Adult neurogenesis – the suggestion that adult brain has the capacity to produce new neurons – was first described by Dr Steve Goldman et al in the 1980s in a study on neuroplasticity in canaries. Songbirds, such as canaries, have the rare ability to lay down new neurons as they learn new songs.

Research in songbirds identified certain proteins including brain-derived neurotrophic factor (BDNF) – that has the role of directing progenitor cells to differentiate to produce neurons.

Additionally, Goldman’s research in mouse models showed these new neurons were generated when BDNF and the protein, Noggin, were delivered to the brain’s progenitor cells. Migrated to the striatum – a motor control region of the brain – they developed into medium spiny neurons cells, which are the major cells to be lost in Huntington’s disease. Benraiss and Goldman have also shown new medium spiny neuron formations could be induced in primates by the same agents.

However, to what extent newly generated medium spiny neurons can be integrated into the brain’s networks remains unclear. Benraiss’ research now demonstrates that the newly generated neurons connect with the complex networks in the brain which are responsible for motor control and can replace the function of those neurons lost by the effects of Huntington’s.

The researchers used a process of genetic tagging so newly created new cells could be followed over time to be able to see newly developed connections.

“In this paper, we used a combination of electrophysiology, optogenetics – alongside mouse behaviour – to show that these cells are not only produced in the adult brain but functionally restore motor circuits in both healthy mice and in the context of Huntington's disease,” said Dr Jose Cano, a postdoctoral associate in the Dr Goldman’s lab and lead author of the study.

The researchers were then able to deploy these technologies in combination to map the connections between the new neurons, their neighbours and other regions of the brain. The use of optogenetics techniques meant the researchers could turn the new cells off and on, to confirm integration into broader brain networks significant to motor control.

The study suggests that treatment for Huntington’s disease might be possible if the brain was encouraged to replace lost cells with new, functional ones in order to restore the communication pathways in the brain.

“Taken together with the persistence of these progenitor cells in the adult primate brain, these findings suggest the potential for this regenerative approach as a treatment strategy in Huntington’s and other disorders characterised by the loss of neurons in the striatum,” said Benraiss.

For further reading please visit: 10.1016/j.celrep.2025.115440