UC San Diego

Experience-dependent expression of immediate-early gene transcription factors can transiently change the transcriptome of active neurons and initiate persistent changes in cellular function. However, the impact of inducible transcription factors (ITFs) on circuit connectivity and function is poorly understood. We investigate the specificity with which the ITF NPAS4 governs experience-dependent changes in inhibitory synaptic input onto CA1 pyramidal neurons (PNs). We show that novel sensory experience selectively enhances somatic inhibition mediated by cholecystokinin-expressing basket cells (CCKBCs) in an NPAS4-dependent manner. NPAS4 specifically increases the number of synapses made onto PNs by individual CCKBCs without altering synaptic properties. Additionally, we find that sensory experience-driven NPAS4 expression enhances the amount of PN inhibition that can be suppressed by depolarization-induced suppression of inhibition (DSI), a short-term form of cannabinoid-mediated plasticity expressed at CCKBC synapses. Our results indicate that CCKBC inputs are a major target of the NPAS4-dependent transcriptional program in PNs, and consequently that NPAS4 is an important regulator of cannabinoid-sensitive inhibition in the hippocampus.