BDNF plays numerous important roles in brain development and plasticity by affecting the development and function of synapses. The expression of BDNF is exquisitely sensitive to neuronal activity, and transcriptional regulation of BDNF synthesis is the major mode of activity-dependent BDNF induction. Thus, the study of BDNF transcription can offer important insights into synapse to nucleus to synapse signaling. We have used behavioral and biochemical analysis of knockout mice to study the role of the unique transcription factor Calcium-Response Factor (CaRF) in this process, revealing that the regulation of BDNF by CaRF is selective for specific brain regions and stimulus conditions. In related, ongoing studies in the lab, we have identified additional transcriptional targets of CaRF that suggest a role for this transcription factor in the regulation of neuronal signaling cascades that underlie homeostatic synaptic plasticity. We are also continuing to identify new transcriptional regulators of the BDNF gene with the goal of understanding mechanisms of stimulus-selective regulation of immediate-early genes in neurons.