Mechanisms of neuron-astrocyte signaling underlying synapse formation and function
There are three sub-projects that study the proteins secreted by astrocytes and GABAergic neurons that affects axon length, branching and inhibitory synapse formation:
- determine how astrocyte soluble signals affect inhibitory axon outgrowth, branching and synaptogenesis in vitro and in brain slices;
- test candidate soluble proteins for their role in inhibitory axon outgrowth, branching and synaptogenesis; and
- identify soluble signals released by astrocytes that increase inhibitory axon outgrowth, branching and synaptogenesis. We are taking a proteomics-based approach, in collaboration with Harry Ischiropoulos, Ph.D.
A related project is based on our observation that neuron-astrocyte contact is required for the excitatory and inhibitory neurons formed in culture to become functional. We are using similar approaches to:
- determine how presynaptic terminals functionally mature during development, and
- to identify the contact-mediated signals that underlie functional maturation of presynaptic terminals.
The results of these experiments will allow us to determine the molecular mechanisms underlying astrocyte-neuron signaling that mediate inhibitory axon length, branching and synaptogenesis. Understanding of how inhibitory synapses are formed during neural development may also contribute to understanding of disorders of development such as epilepsy, autism and mental retardation.