NPAS4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus

eLife

Anja Payne¹  Kelly M Martyniuk²  Brenda L Bloodgood³  Daniel A Heinz³  G Stefano Brigidi³  Nathalie A Djaja³  Andrea L Hartzell⁴ 

[1] Biological Sciences 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;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;

关键词: NPAS4;    immediate early gene transcription factor;    CCK basket cell;    DSI;    CA1 pyramidal neuron;   

DOI  :  10.7554/eLife.35927

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown