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Loss of HCN2 in Dorsal Hippocampus of Young Adult Mice Induces Specific Apoptosis of the CA1 Pyramidal Neuron Layer.
Deutsch, Matthias; Stegmayr, Carina; Balfanz, Sabine; Baumann, Arnd.
Afiliação
  • Deutsch M; Research Center Jülich, Institute of Biological Information Processing, IBI-1, 52428 Jülich, Germany.
  • Stegmayr C; Department of Biology, University of California, San Diego, La Jolla, CA 92083, USA.
  • Balfanz S; Research Center Jülich, Institute of Neuroscience and Medicine, INM-4, 52428 Jülich, Germany.
  • Baumann A; Research Center Jülich, Institute of Biological Information Processing, IBI-1, 52428 Jülich, Germany.
Int J Mol Sci ; 22(13)2021 Jun 22.
Article em En | MEDLINE | ID: mdl-34206649
ABSTRACT
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 Ih-current that contributes to various aspects of neural signaling. In mammals, four genes (hcn1-4) 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 hcn2 gene expression both in vitro and in vivo. Electrophysiological measurements showed that HCN2 subunit knock-down resulted in specific yet anticipated changes in Ih-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 hcn2 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Canais de Potássio / Apoptose / Células Piramidais / Região CA1 Hipocampal / Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização / Hipocampo Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Canais de Potássio / Apoptose / Células Piramidais / Região CA1 Hipocampal / Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização / Hipocampo Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article