This study will determine the feasibility of using cellular imaging in mice to determine whether embryonic brain cells that are transplanted into the cerebral cortex integrate into neural networks and functionally replace the brain cells that have died, or at least help to reorganize the neural networks. If feasibility is established, this imaging method could be used to develop refinements for improving transplantation therapy.
Inhibitory neurons normally suppress excessive brain activity. They are selectively damaged or killed in several brain diseases, such as epilepsy and prion disease (e.g., Creutzfeldt-Jacob disease). Recent research has demonstrated that new brain cells can be generated, but inhibitory neurons cannot be sufficiently generated in the cerebral cortex to offset the loss of these activity-suppressing cells. Transplantation of inhibitory neurons from a region of the embryonic brain where they develop, called the “medial ganglionic eminence,” is a promising therapeutic alternative. A major question, however, is whether or not the transplanted cells will integrate into the neural networks of the cells that they are replacing, or whether the transplanted cells will at least help to reorganize these networks into newly functioning neural circuits.
The researchers previously showed that normally functioning inhibitory neurons are crucial for enabling the visual cortex to reorganize its responses and connections as result of experience. If inhibitory neurons are transplanted into mice that have been bred to have insufficient numbers of these brain cells, the transplanted cells may be able to restore brain plasticity (the ability to form new connections) in these mice. As a first step towards determining whether this is the case, the investigators will transplant young neurons from the medial ganglionic eminence of embryonic mice into the visual cortex of the adult mouse. Then the researchers will use two-photon cellular imaging to assess the transplanted cells’ integration into brain tissue. If so, this will pave the way for further studies to determine whether the transplanted cells make functionally normal connections.
Significance: If successful, this research approach could lead to improved methods for developing and evaluating transplantation therapies for epilepsy and similar diseases that deplete inhibitory brain cells.