Cellular and Molecular Neurobiology
Neuroscience Laboratories , Graduate School of Frontier Biosciences
Nobuhiko Yamamoto, Ph.D.
We are interested in how neuronal connections are formed during development of the brain. It has been suggested that fundamental patterns of neuronal circuits are established by a precise developmental program whereas fine connections are modified by electrical activity including spontaneous firing. We are exploring cellular and molecular mechanisms that underlie these processes, focusing on neocortical connections.
1. Laminar specific connections
One of the characteristic features in cortical connections is layer specificity. The neocortex is composed of six cell layers, by which extrinsic and intrinsic cortical connections are organized. In particular the thalamocortical projection is well characterized in terms of laminar specificity and development. During development sensory thalamocortical axons travel through the specific pathways, enter the cortical plate, pass through the deep cortical layers and finally project to layer 4. How thalamocortical axons recognize the target layer?
Previous in vitro studies with organotypic coculture preparations have demonstrated that thalamic axons exhibit stopping and branching behavior in the target layer. Moreover, evidence indicates that stopping is attributable to the inhibitory activity (partly due to glycosylphosphatidylinositol-linked molecules) in the upper cortical layers, whereas lamina-specific branching is regulated by a positive factor (unknown) in the target layer and an inhibitory component (polysialylated neural cell adhesion molecule) in all cortical layers. To reveal the molecular mechanisms that are responsible for axonal stopping and branching behaviors, we attempt to identify the genes that are expressed specifically in layer 4 or in the upper layers.
2. Intrinsic cortical connections
Cortical neurons in the upper layers are known to project axons to the same layers as well as the contralateral hemisphere. This horizontal projection has been shown to contain additive and retractive processes of axonal growth and branching. Evidence further suggests that electrical activity of cortical neurons are involved in these processes. We recently began to study how horizontal axon behaviors are regulated by electrical activity, by monitoring and manipulating neuronal activity in organotypic slice cultures.