@ARTICLE{10.3389/fnmol.2012.00031, AUTHOR={Delgado, Jary and Owens, Geoffrey}, TITLE={The cytochrome c gene proximal enhancer drives activity-dependent reporter gene expression in hippocampal neurons}, JOURNAL={Frontiers in Molecular Neuroscience}, VOLUME={5}, YEAR={2012}, URL={https://www.frontiersin.org/articles/10.3389/fnmol.2012.00031}, DOI={10.3389/fnmol.2012.00031}, ISSN={1662-5099}, ABSTRACT={The proximal enhancer of the cytochrome c gene (Cycs) contains binding sites for both cAMP response element binding proteins (CREB) and Nuclear Respiratory Factor 1 (NRF1). To investigate how neuronal activity regulates this enhancer region, a lentivirus was constructed in which a short-lived green fluorescent protein (GFP) was placed under the transcriptional control of the Cycs proximal enhancer linked to a synthetic core promoter. Primary hippocampal neurons were infected, and the synaptic strengths of individual neurons were measured by whole-cell patch clamping. On average the amplitude of miniature postsynaptic currents (mEPSCs) was higher in brighter GFP+ neurons, while the frequency of mEPSCs was not significantly different. Increasing neural activity by applying a GABAA receptor antagonist increased GFP expression in most neurons, which persisted after homeostatic synaptic scaling as evidenced by a decrease in the amplitude and frequency of mEPSCs. Removing the CREB binding sites revealed that calcium influx through L-type channels and NMDA receptors, and ERK1/2 activation played a role in NRF1-mediated transcription. CREB and NRF1, therefore, combine to regulate transcription of Cycs in response to changing neural activity.} }