The nervous system consists of multiple cell types with distinct physiological specializations and gene expression patterns. In tissue, these cells form a complex, intertwined network that is subject to constant interaction between different cell types. This complexity poses a challenge for researchers in both separating cell types for analysis as well as studying interactions and information transfer between cells. In this application, we propose a molecular neuroscience study addressing both aspects. First, we are developing proteomics methods to allow analysis of newly synthesized proteins on a cell type-specific basis. Second, we shall use novel genetic tools for cell type-specific stimulation and gene expression analysis in primary co-cultures of neurons and astroglial cells. We shall use this system to probe gene expression signatures in neuron-astrocyte communication and determine the transmitters that form the basis of this communication.
Formation of new synapses, and alteration of the strength and stability of existing synapses are regarded as the main cellular basis for memory and long-term behavioral adaptations. Neuronal activity-regulated gene expression plays a crucial role in synaptic development and function, and its deregulation gives rise to various nervous system disorders. Knowledge about the regulatory mechanisms of activity-dependent gene expression is important both for understanding of nervous system function and for finding new drug targets. The aim of this project is to study the molecular mechanisms of neuronal activity-regulated gene expression, including transcription, translation and posttranslational modifications, in the nervous system health and disease. The studies are focused on two genes, the neurotrophin BDNF and the basic helix-loop-helix transcription factor TCF4.