HCN4 knockdown in dorsal hippocampus promotes anxiety‐like behavior in mice

Anne Günther; Vincent Luczak; Nadine Gruteser; Ted Abel; Arnd Baumann

doi:10.1111/gbb.12550

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HCN4 knockdown in dorsal hippocampus promotes anxiety‐like behavior in mice

Journal article

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HCN4 knockdown in dorsal hippocampus promotes anxiety‐like behavior in mice

Anne Günther, Vincent Luczak, Nadine Gruteser, Ted Abel and Arnd Baumann

Genes, brain and behavior, Vol.18(2), pp.e12550-n/a

02/2019

DOI: 10.1111/gbb.12550

PMCID: PMC6850037

PMID: 30585408

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Abstract

Hyperpolarization‐activated and cyclic nucleotide‐gated (HCN) channels mediate the Ih current in the murine hippocampus. Disruption of the Ih current by knockout of HCN1, HCN2 or tetratricopeptide repeat‐containing Rab8b‐interacting protein has been shown to affect physiological processes such as synaptic integration and maintenance of resting membrane potentials as well as several behaviors in mice, including depressive‐like and anxiety‐like behaviors. However, the potential involvement of the HCN4 isoform in these processes is unknown. Here, we assessed the contribution of the HCN4 isoform to neuronal processing and hippocampus‐based behaviors in mice. We show that HCN4 is expressed in various regions of the hippocampus, with distinct expression patterns that partially overlapped with other HCN isoforms. For behavioral analysis, we specifically modulated HCN4 expression by injecting recombinant adeno‐associated viral (rAAV) vectors mediating expression of short hairpin RNA against hcn4 (shHcn4) into the dorsal hippocampus of mice. HCN4 knockdown produced no effect on contextual fear conditioning or spatial memory. However, a pronounced anxiogenic effect was evident in mice treated with shHcn4 compared to control littermates. Our findings suggest that HCN4 specifically contributes to anxiety‐like behaviors in mice. Knockdown of HCN4 in the dorsal hippocampus of mice specifically affects anxiety‐like behaviors.

rAAV

rAAV9

anxiety

elevated zero maze

RNAi

fear conditioning

shRNA

spatial object recognition

locomotor activity

open field test

injection

HCN channels

Details

Title: Subtitle: HCN4 knockdown in dorsal hippocampus promotes anxiety‐like behavior in mice
Creators: Anne Günther - Institute of Complex Systems, Cellular Biophysics (ICS‐4),Research Center Jülich
Vincent Luczak - University of California
Nadine Gruteser - Institute of Complex Systems, Cellular Biophysics (ICS‐4),Research Center Jülich
Ted Abel - University of Iowa Carver College of Medicine
Arnd Baumann - Institute of Complex Systems, Cellular Biophysics (ICS‐4),Research Center Jülich
Resource Type: Journal article
Publication Details: Genes, brain and behavior, Vol.18(2), pp.e12550-n/a
DOI: 10.1111/gbb.12550
PMID: 30585408
PMCID: PMC6850037
NLM abbreviation: Genes Brain Behav
ISSN: 1601-1848
eISSN: 1601-183X
Publisher: Blackwell Publishing Ltd; Oxford, UK
Number of pages: 12
Grant note: National Science Foundation (NSF 1515458) Directorate for Biological Sciences (NSF 151548)
Language: English
Date published: 02/2019
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984070736402771

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