The long-term goal of this proposal is to understand the molecular and cellular mechanisms that regulate thedevelopment of cerebellar neuronal circuits. Dendritic spines, sites of synaptic input on many projectionneurons such as the cerebellar purkinje cell are highly dynamic structures and their motility isdevelopmentally regulated. The mechanisms that regulate spine dynamics over development are notknown. Here, we will use multiphoton live imaging of neuronal structures in organotypic slices and in vivo, inconjunction with electron microscopy to study the mechanisms of synaptic maintenance. Our centralhypothesis is that ensheathment by glial processes critically regulates dendritic spine motility andsynapticstability. In the first aim we will characterize the development of Bergmann glia processes using static anddynamics imaging approaches. In the second aim we will test how spine dynamcis is regulated by glialensehathment by measuring spine motility in genetic models with reduced glial ensehthment. In the third aimwe will determine the role of EphA receptors and the ephrin ligands in glia-spine cross talk and regulation ofspine dynamics. Finally, we will determine how synaptic mainetnance is related to spine motility and isregulated by glial processes. Abnormal development of neuronal connections can be the cause ofneurodevelopmental disorders in humans. Moreover, recently it has been demonstrated that abnormal glial-neuron interactions during development might cause mental disorders in the adult. Therefore, understandingthe cellular and molecular mechanisms of glial-neuron interactions during synapseformation andmaintenance has important health significance.
| Dunaevsky, Anna (2012) Neuron-glial interactions in the developing cerebellum. Microsc Microanal 18:742-4 |
| Lippman Bell, Jocelyn J; Lordkipanidze, Tamar; Cobb, Natalie et al. (2010) Bergmann glial ensheathment of dendritic spines regulates synapse number without affecting spine motility. Neuron Glia Biol 6:193-200 |
| Lippman, Jocelyn J; Lordkipanidze, Tamar; Buell, Margaret E et al. (2008) Morphogenesis and regulation of Bergmann glial processes during Purkinje cell dendritic spine ensheathment and synaptogenesis. Glia 56:1463-77 |
