An embryo of the African clawed frog (Xenopus laevis). Photo: Juan J. Segura Sampedro
By placing electrodes on the still-flat neural plate of a frog embryo, researchers have succeeded in measuring brain activity from the earliest stages of development.
Hesearchers have succeeded for the first time in implanting ultra-flexible electrodes into the brain of a frog during embryonic development, without disrupting normal brain development. This allows them to continuously measure brain activity from individual nerve cells in a developing animal. In their study published on 11 June in Nature , bioengineers at Harvard University report that their findings pave the way for a new generation of bioelectronics that adapt to the brain. The electrodes, made from an ultra-thin network of soft, stretchable material, are applied to the flat neural plate of an embryo before it folds into the tubular central nervous system. During organogenesis, the electrodes deform along with the folding tissue and spread throughout the developing brain, becoming fully integrated into the three-dimensional brain structure.
‘By exploiting the brain’s natural 2D-to-3D growth process, a stable, integrated interface is created without implantation causing damage,’ the authors write. They found no evidence of abnormalities in the implanted embryos: the animals developed normally, showed no notable gene activity, and behaved like the controls.
Damage
This matters, because brain implants typically cause damage to neural tissue, however small or soft they may be. This is particularly problematic in rapidly developing brains, such as those of embryos. Until now, it had not been possible to continuously monitor brain activity in living animals from the embryonic stage onwards. This technique makes it possible: the researchers measured brain signals in African clawed frog embryos (Xenopus laevis) with a precision of a few milliseconds, from both individual neurons and networks.
Amputation
They then tested the method on embryos of the axolotl, a salamander renowned for its regenerative capacity. They observed that brain activity changed following amputation of the tail, indicating a neural response to injury elsewhere in the body. In a subsequent step, they stimulated the same brain regions via the electrodes. This accelerated tail regeneration, suggesting that the brain actively contributes to the recovery process.
Compatible
The researchers expect their approach to be applicable in mammals as well. Initial experiments showed the electrodes to be compatible with mouse embryos and newborn rats. Because the basic principles of brain development are largely conserved across vertebrates, the authors believe the platform may prove applicable in other mammalian models in follow-up studies – for example, for fundamental research into human developmental disorders.