The current view of brain development is that neuronal circuits are formed through an interaction between two fundamentally different mechanisms. First, growing axons are targeted to specific regions by molecular guidance and recognition cues. Second, on going neuronal activity regulates the strength and position of synapses to fine-tune the connectivity pattern. Although this general scheme is well known, little detailed knowledge exists about how specific patterns of circuitry characteristic of differe nt brain regions arise.
During embryonic development of the brain, activity patterns are anything but specific. Instead, waves of activity spread through large areas, activating vast numbers of neurons synchronously. These spontaneous depolarizing waves resemble epileptiform activity in the mature brain, and are believed somehow to be involved in regulating the maturation of synapses. Over time, this spontaneous global network activity diminishes and resolves into the more discrete patterns of activity found in functionally specific neuronal circuits.
Most studies of spontaneous activity at early stages have used recording techniques that do not discriminate among the many neuron populations that are found in any given brain region. In this project, we propose to follow very specific neuronal circuits from the stages when spontaneous global activity predominates, to their maturation as relatively distinct circuits. We will use techniques for optical recording of neuronal activity that can provide an ac curate picture of how these specific circuits emerge from the background of embryonic interconnectivity. This will provide important new information about the dynamic development of brain circuits, with implications for our understanding of the developme nt of behavior and of behavioral disturbances. The proposed research thus bears a potential impact on concepts of normal and abnormal neurological and psychological development in children.