Decoding the function of an inducible transcription factor in pyramidal neurons
Brenda Bloodgood, PhD
Assistant Professor, Division of Biological Science, Section of Neurobiology, University of California, San Diego
Host: Greg Bieri (Gitler Lab)
In neurons, inducible transcription factors (ITFs) are expressed in response to membrane depolarization and are essential for morphological, synaptic and circuit plasticity. Because of this, ITFs are routinely used to identify behaviorally-relevant neurons in vivo. Yet, it remains unclear if an ITF can convey information to the nucleus about select features of a circuit’s activity or alter how that neuron is functionally embedded within the local circuit. To address these questions I will first describe two pathways, spatially segregated within hippocampal CA1 pyramidal neurons, which allow the ITF Npas4 to independently report changes in synaptic inputs from CA3 and the neuron’s action potential output to the nucleus. These pathways emerge from the regulation of Npas4 mRNA transcription, trafficking, and translation that are tailored at each step to support the detection of changes in synaptic or action potentials. Finally, I will share our insights into the functional consequences of Npas4 expression. We find Npas4 promotes the formation of inhibitory synapses made specifically by CCK basket cells. This results in enhanced cannabinoid-mediated short-term plasticity and likely improves the signal to noise in the synaptic computations executed by the pyramidal neuron.
 Yingxi Lin, Brenda L. Bloodgood, Jessica L. Hauser, Ariya D. Lapan, Alex C. Koon, Tae-Kyung Kim, Linda S. Hu, Athar N. Malik, and Michael E. Greenberg. Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 2008; 455: 1198-1204. doi:10.1038/nature07319
 Brenda L. Bloodgood, Nikhil Sharma, Heidi Adlman Browne, Alissa Z. Trepman & Michael E. Greenberg. The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature (2013) 121:125. doi:10.1038/nature12743