Grant: Project Grant

Brain circuits follow a step-by-step development that in mammals starts in the embryo. Two cell classes are at the core of how brains function: 1) Excitatory and 2) Inhibitory neurons. These two cell classes connect with each other during embryonic development to form neuronal circuits. The formation of neuronal circuits is assisted by communication between neurons. In this proposal, we aim to understand the initial development of neuronal circuits that include both excitatory and inhibitory neurons in the neocortex - a brain region that is thought to be involved in generating higher order functions such as consciousness. To study the initial development of neuronal circuits with microscopy, I developed a technique that stabilizes mouse embryos while they are still connected to their mothers via the umbilical cord. This was the first time that brain development was observed in living mammalian embryos with a resolution that allows us to see the components of a single neuron that are important for communication, including their axons, dendrites and synapses. We will exploit this approach to ask key questions: 1) When do excitatory neurons and inhibitory neurons connect and communicate in neocortex, 2) How do excitatory neurons and inhibitory neurons in neocortex communicate at their inception, and 3) How does the communication between excitatory neurons and inhibitory neurons in the neocortex assist with their proper development. This work is important because it will greatly advance our understanding of brain development and function, and because problems in the step-by-step development of these circuits are strongly implicated in neurodevelopmental disorders such as autism, schizophrenia and some forms of epilepsy.