Neuroscience Graduate Program, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States; Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States
Kelly M Martyniuk
Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States
G Stefano Brigidi
Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States
Daniel A Heinz
Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States; Biological Sciences Graduate Program, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States
Nathalie A Djaja
Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States
Anja Payne
Neuroscience Graduate Program, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States; Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States
Neuroscience Graduate Program, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States; Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States
Experience-dependent expression of immediate-early gene transcription factors (IEG-TFs) can transiently change the transcriptome of active neurons and initiate persistent changes in cellular function. However, the impact of IEG-TFs on circuit connectivity and function is poorly understood. We investigate the specificity with which the IEG-TF 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 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 that NPAS4 is an important regulator of plasticity mediated by endogenous cannabinoids.
