We all know that it is easier to learn a new language or musical instrument as a child rather than in adulthood. At no other time in life does the surrounding environment so potently shape brain function – from basic motor skills and sensation to higher cognitive processes like language – than it does during childhood. This experience-dependent process occurs at distinct time windows called “critical periods”, which are times of great opportunity but also of great vulnerability for the developing brain. Early disruption of proper sensory or social experiences will result in mis-wired circuits that will respond sub-optimally to normal experiences in the future. Comparable effects are also seen for the development of vision, where if a child’s binocular vision is compromised and not corrected before the age of eight, amblyopia (‘lazy eye’) is permanent and irreversible.
One of the most exciting developments in neuroscience in the last 10 years has been new insights into the biology of neuroplasticity, which refers to the brain’s ability to learn, adapt, and rewire itself. Until recently we thought neuroplasticity was limited to a critical period in childhood, and that the window was largely closed by adulthood. That meant that many neurodevelopmental disorders were almost untreatable in adults. But neuroscientists have come to understand that we can actually reopen that critical period later in life. Hirofumi Morishita Laboratory in Friedman Brain Institute and the Mindich Child Health and Development Institute uses the visual system to identify the molecular mechanisms that govern neuroplasticity and explores how those mechanisms can be applied to the adult brain for therapeutic intervention.
We’re looking at a molecule called Lynx1, which acts as a ‘brake’ that limits neuroplasticity. In our previous investigations, we conducted animal model studies of the visual disorder ambylopia, and established that by removing Lynx1, we could reintroduce plasticity and restore normal vision. We also found that an existing drug used to treat Alzheimer’s disease has an opposite action to Lynx1 and could have possible therapeutic value for ambylopia; that finding is now being tested in an early clinical trial.
Using Lynx1 as our basis, we’re expanding our map of the molecular network that regulates plasticity. In collaboration with Joel Dudley Laboratory in the Icahn Institute of Genomics and Multiscale Biology, we introduce computational approach to systematically identify new class of drugs to enhance neuroplasticity. This allows us to find better, more robust drugs to enhance brain plasticity and to improve therapies for neurodevelopmental disorders from autism to schizophrenia.
Hirofumi Morishita, MD
Assistant Professor of Psychiatry, Neuroscience and Ophthalmology, Icahn School of Medicine at Mount Sinai