Neuronal Activity-Dependent Regulation of Gene Expression
Neuronal activity induces transcription of a large set of genes, many of which encode proteins that function at synapses. Transcriptional regulation of these gene products constitutes a mechanism for the use-dependent modification of synapses that is likely to contribute to synaptic plasticity both during development and in the adult brain.

Significant insights into the mechanisms and functions of activity-dependent transcription have come from studies of the gene encoding Brain-Derived Neurotrophic Factor (BDNF).  BDNF is a secreted protein of the neurotrophin family that has numerous functions in the nervous system including the promotion of neuronal survival and the modulation of synaptic function. Neuronal activity drives robust transcription at the Bdnf gene locus, providing a useful assay to identify molecular mechanisms that mediate the transcriptional response to neuronal activity. Several ongoing projects in our laboratory have grown out of our studies of Bdnf transcription including:

• Functional characterization of the novel transcription factor CaRF using bioinformatics to identify CaRF target genes and microarray analysis of gene expression profiles in CaRF knockout mice.

• Molecular mechanisms and functional implications of dendritic targeting of Bdnf mRNA splice variants.

We use transfection of low density neuronal cultures to study how gene manipulation in single cells affects the process of synapse formation.
The image above shows a GFP-transfected neuron (green) grown in culture on a bed of underlying glial cells (labeled for GFAP in blue). Synapses are labeled for synapsin I (red).