Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer
Neurons inevitably rely on a proper repertoire and distribution of membrane-bound ion-conducting channels. Among these proteins, the family of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels possesses unique properties giving rise to the corresponding I<sub>h</sub>...
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doaj-975984484be54bcfbb76c5ce1dbf77cc2021-07-15T15:36:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226699669910.3390/ijms22136699Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron LayerMatthias Deutsch0Carina Stegmayr1Sabine Balfanz2Arnd Baumann3Research Center Jülich, Institute of Biological Information Processing, IBI-1, 52428 Jülich, GermanyResearch Center Jülich, Institute of Neuroscience and Medicine, INM-4, 52428 Jülich, GermanyResearch Center Jülich, Institute of Biological Information Processing, IBI-1, 52428 Jülich, GermanyResearch Center Jülich, Institute of Biological Information Processing, IBI-1, 52428 Jülich, GermanyNeurons inevitably rely on a proper repertoire and distribution of membrane-bound ion-conducting channels. Among these proteins, the family of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels possesses unique properties giving rise to the corresponding I<sub>h</sub>-current that contributes to various aspects of neural signaling. In mammals, four genes (<i>hcn1-4</i>) encode subunits of HCN channels. These subunits can assemble as hetero- or homotetrameric ion-conducting channels. In order to elaborate on the specific role of the HCN2 subunit in shaping electrical properties of neurons, we applied an Adeno-associated virus (AAV)-mediated, RNAi-based knock-down strategy of <i>hcn2</i> gene expression both in vitro and in vivo. Electrophysiological measurements showed that HCN2 subunit knock-down resulted in specific yet anticipated changes in I<sub>h</sub>-current properties in primary hippocampal neurons and, in addition, corroborated that the HCN2 subunit participates in postsynaptic signal integration. To further address the role of the HCN2 subunit in vivo, we injected recombinant (r)AAVs into the dorsal hippocampus of young adult male mice. Behavioral and biochemical analyses were conducted to assess the contribution of HCN2-containing channels in shaping hippocampal network properties. Surprisingly, knock-down of <i>hcn2</i> expression resulted in a severe degeneration of the CA1 pyramidal cell layer, which did not occur in mice injected with control rAAV constructs. This finding might pinpoint to a vital and yet unknown contribution of HCN2 channels in establishing or maintaining the proper function of CA1 pyramidal neurons of the dorsal hippocampus.https://www.mdpi.com/1422-0067/22/13/6699Adeno-associated virus (AAV)hyperpolarization-activated and cyclic nucleotide-gated ion channel (HCN-channel)immunocytochemistryknock-downpacemaker channelpatch-clamp |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthias Deutsch Carina Stegmayr Sabine Balfanz Arnd Baumann |
spellingShingle |
Matthias Deutsch Carina Stegmayr Sabine Balfanz Arnd Baumann Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer International Journal of Molecular Sciences Adeno-associated virus (AAV) hyperpolarization-activated and cyclic nucleotide-gated ion channel (HCN-channel) immunocytochemistry knock-down pacemaker channel patch-clamp |
author_facet |
Matthias Deutsch Carina Stegmayr Sabine Balfanz Arnd Baumann |
author_sort |
Matthias Deutsch |
title |
Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer |
title_short |
Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer |
title_full |
Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer |
title_fullStr |
Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer |
title_full_unstemmed |
Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer |
title_sort |
loss of hcn2 in dorsal hippocampus of young adult mice induces specific apoptosis of the ca1 pyramidal neuron layer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-06-01 |
description |
Neurons inevitably rely on a proper repertoire and distribution of membrane-bound ion-conducting channels. Among these proteins, the family of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels possesses unique properties giving rise to the corresponding I<sub>h</sub>-current that contributes to various aspects of neural signaling. In mammals, four genes (<i>hcn1-4</i>) encode subunits of HCN channels. These subunits can assemble as hetero- or homotetrameric ion-conducting channels. In order to elaborate on the specific role of the HCN2 subunit in shaping electrical properties of neurons, we applied an Adeno-associated virus (AAV)-mediated, RNAi-based knock-down strategy of <i>hcn2</i> gene expression both in vitro and in vivo. Electrophysiological measurements showed that HCN2 subunit knock-down resulted in specific yet anticipated changes in I<sub>h</sub>-current properties in primary hippocampal neurons and, in addition, corroborated that the HCN2 subunit participates in postsynaptic signal integration. To further address the role of the HCN2 subunit in vivo, we injected recombinant (r)AAVs into the dorsal hippocampus of young adult male mice. Behavioral and biochemical analyses were conducted to assess the contribution of HCN2-containing channels in shaping hippocampal network properties. Surprisingly, knock-down of <i>hcn2</i> expression resulted in a severe degeneration of the CA1 pyramidal cell layer, which did not occur in mice injected with control rAAV constructs. This finding might pinpoint to a vital and yet unknown contribution of HCN2 channels in establishing or maintaining the proper function of CA1 pyramidal neurons of the dorsal hippocampus. |
topic |
Adeno-associated virus (AAV) hyperpolarization-activated and cyclic nucleotide-gated ion channel (HCN-channel) immunocytochemistry knock-down pacemaker channel patch-clamp |
url |
https://www.mdpi.com/1422-0067/22/13/6699 |
work_keys_str_mv |
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