Synaptic development of the retinogeniculate pathway

PROJECT SUMMARY Throughout childhood, individual neurons that make up our brain form connections, or circuits, between each other. These circuits guide the flow of activity across our brain for proper functioning. A fascinating feature of the brain is that it’s believed that both our genetics and our experiences as children can influence how neurons connect to each other. Understanding this process is critical to knowing how our childhood experiences influence brain development, and how disruptions in this process result in neurodevelopmental disabilities like Autism. Surprisingly, despite its importance, we have very little direct data on how these physical connections form during childhood development. Rather, our understanding of this process is largely based on interpretations of data that do not directly follow how neurons connect with each other. This is because until recently, these kinds of experiments were difficult if not impossible to do. However, our lab has developed technology that now allows us to investigate how circuits form in a clear and unambiguous way. With these new tools we will first ask how neurons make the correct connections during development by focusing on a well-studied circuit between the eyes and the brain. This circuit will allow us to ask how connections between the left and right eye properly form in concert together to ensure that what our eyes see gets correctly processed in the brain. In the second aim, we will ask how closing one eye, which will block activity, or visual “experiences” from that eye, disrupts this process. We believe that what we learn from studying this visual circuitry will provide clues to how neurons form circuits throughout the brain. We will conduct these experiments in the ferret because there is a lot of existing data on how this visual circuit develops in this animal that we can use to better interpret our results. Additionally, the ferret visual circuit and its brain more closely resembles the human brain relative to mice, another popular model organism in neuroscience. This will make it more likely that the lessons we learn in the ferret will also be true in humans. Overall, we believe results from our proposal will help better understand how brain connections form during childhood which may inform how much we need to worry about the environment our children grow up in. Our proposal might also help with treating neurodevelopmental disabilities by providing additional evidence for treating conditions early in life while the brain is forming new connections and is still amenable to therapies.