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Elife. 2018 Jul 27;7. pii: e35927. doi: 10.7554/eLife.35927.

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

Author information

1
Neuroscience Graduate Program, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States.
2
Division of Biological Sciences, Section of Neurobiology, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States.
3
Biological Sciences Graduate Program, Center for Neural Circuits and Behavior, University of California San Diego, San Diego, United States.

Abstract

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.

KEYWORDS:

CA1 pyramidal neuron; CCK basket cell; DSI; NPAS4; immediate early gene transcription factor; mouse; neuroscience

PMID:
30052197
PMCID:
PMC6105310
DOI:
10.7554/eLife.35927
[Indexed for MEDLINE]
Free PMC Article

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