With RSO-Funded Researcher Dr. Michaela Fagiolini

Michaela FagioliniDr. Fagiolini is studying how neurons in the cortex of the brain change during the onset and progression of Rett syndrome and how they change in response to Ketamine treatment. The cortex is the area of the brain that receives sensory information – sight, taste, smell, sound and touch. Rett syndrome alters the way the neurons process this sensory information.
Ketamine is a drug that has been used to treat other disorders and is being studied as a potential treatment for Rett syndrome. Dr. Fagiolini’s work will help lay the groundwork to determine proper ketamine dosing and help set parameters to evaluate ketamine’s effectiveness in Rett syndrome.

Dr. Fagiolini will image the brains of RTT mice as they respond to visual sensory information. She will compare the changes at the onset of RTT to changes after regression from RTT has begun. She will then image the brains after ketamine dosing to see its effect. This information will be used to determine the optimal dosage needed to re-establish proper function of neurons in the cortex. This work is being done on female RTT mice with a Mecp2 mutation. These mice have symptoms similar to the human condition. Because of this, Dr. Fagiolini says that the outcomes from this study will be immediately translated in the clinical setting and will help shape upcoming clinical trials.

The Hope

Dr. Fagiolini’s goal is to see how the RTT brain responds to sensory input from the environment, giving a better understanding of how abnormalities in the neuron networks of the cortex can be corrected. They will also measure the effectiveness of ketamine intervention on those networks, and determine the optimal dosage needed to re-establish proper function.
This will pave the way for the development of future ketamine clinical trials and additional treatments for Rett syndrome.

The Answers to your Questions

The Researcher

Dr. Michela Fagiolini is an Associate Professor in the Department of Neurology at Boston Children’s Hospital, where she had launched her research on neurodevelopmental disorders and in particular Rett Syndrome. Her laboratory has an active collaboration with the Boston Rett Syndrome clinic and the laboratory of Cognitive Neuroscience.

Dr. Michela Fagiolini was awarded a Basic Research Award for the project “Two-photon imaging of excitatory/inhibitory cortical activity in mosaic Mecp2 female animal model”. To better understand what is happening inside the lab, we answer some common questions about this research below.

The goal at the end of the two-year project

Dr. Fagiolini and her lab hope to have a better understanding of how the expression or absence of MeCP2 impacts the neuronal activity of excitatory or inhibitory cortical circuits during regression and recovery in the visual cortex of RTT female mice. The experiment proposed here will allow them to directly visualize how brain cells are expressing or lacking MeCP2 change their ability to communicate and properly function during the progression of the disorder. They will also be able to understand better how pharmacological or genetic interventions affect the neurons and their ability to recover and to what degree.

For the scientific abstract of this project, click here.