HCN2 channels in local inhibitory interneurons constrain LTP in the hippocampal direct perforant path.

Cellular and Molecular Life Sciences : CMLS
Lucas MattThomas Kleppisch

Abstract

Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1 pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2(-/-)) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons in wild-type but not HCN2(-/-) mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons.

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Citations

Oct 11, 2014·Progress in Neuro-psychopharmacology & Biological Psychiatry·Mei ZhouLian-Jun Guo
Dec 4, 2012·Journal of Molecular Neuroscience : MN·Bermary Santos-VeraCarlos A Jiménez-Rivera
Oct 24, 2012·The Journal of Physiology·Holger LercheAngela Vincent
Dec 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Qizong YangRobert D Hawkins
Mar 27, 2012·Neuropharmacology·Mala M ShahKatiuscia Martinello
Dec 27, 2018·Genes, Brain, and Behavior·Anne GüntherArnd Baumann
Nov 10, 2017·The EMBO Journal·Dhrubajyoti ChowdhuryJohannes W Hell
Aug 22, 2018·Frontiers in Molecular Neuroscience·Lucas MattWibke Singer
Jun 25, 2019·Frontiers in Molecular Neuroscience·Xiaoli ChangJunxia Xie
Feb 12, 2020·Neuroscience and Biobehavioral Reviews·Elentina K ArgyrousiJos Prickaerts
Jul 3, 2021·International Journal of Molecular Sciences·Matthias DeutschArnd Baumann
Oct 20, 2021·Cellular and Molecular Life Sciences : CMLS·Lucas MattRobert Lukowski

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