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Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex

View ORCID ProfileWei Cai, Shu-Su Liu, Bao-Ming Li, Xue-Han Zhang
doi: https://doi.org/10.1101/2021.05.23.445332
Wei Cai
aInstitute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China
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  • ORCID record for Wei Cai
Shu-Su Liu
aInstitute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China
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Bao-Ming Li
bCenter for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China
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Xue-Han Zhang
aInstitute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China
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  • For correspondence: xuehanzhang@fudan.edu.cn
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Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in neurons in the central nervous system. It has been documented that HCN channels regulate the intrinsic excitability of pyramidal cells in the medial prefrontal cortex (mPFC) of rats. Here, we report that HCN channels limited GABAergic transmission onto pyramidal cells in the mPFC. Pharmacological block of HCN channels resulted in a significant increase in the frequency of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs) in mPFC pyramidal cells. Such facilitation effect on mIPSCs required presynaptic Ca2+ influx and reversed by high-dose cAMP. Such facilitation did not exist in the presence of the T-type Ca2+ channel selective blockers. Immunofluorescence staining revealed that HCN channels expressed in presynaptic GABAergic terminals, as well as in both soma and neurite of parvalbumin-expressing (PV-expressing) basket cells in the mPFC. The present results indicate that HCN channels in GABAergic interneurons, most likely PV-expressing basket cells, constrain inhibitory control over layer 5-6 pyramidal cells through restricting presynaptic Ca2+ entry.

Competing Interest Statement

The authors have declared no competing interest.

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Posted May 23, 2021.
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Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex
Wei Cai, Shu-Su Liu, Bao-Ming Li, Xue-Han Zhang
bioRxiv 2021.05.23.445332; doi: https://doi.org/10.1101/2021.05.23.445332
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Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex
Wei Cai, Shu-Su Liu, Bao-Ming Li, Xue-Han Zhang
bioRxiv 2021.05.23.445332; doi: https://doi.org/10.1101/2021.05.23.445332

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