Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.
Voltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is rest...
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doaj-04567f69fe074b20ba9c52c3529e89ad2021-03-03T22:47:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7859810.1371/journal.pone.0078598Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.Robert Theodor MallmannClaudio ElguetaFaten SlemanJan CastonguayThomas WilmesArn van den MaagdenbergNorbert KlugbauerVoltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V)2.1 mouse models. Global Ca(V)2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V)2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V)2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V)2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V)2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V)2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V)2.1 in the adult murine forebrain.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24205277/pdf/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robert Theodor Mallmann Claudio Elgueta Faten Sleman Jan Castonguay Thomas Wilmes Arn van den Maagdenberg Norbert Klugbauer |
spellingShingle |
Robert Theodor Mallmann Claudio Elgueta Faten Sleman Jan Castonguay Thomas Wilmes Arn van den Maagdenberg Norbert Klugbauer Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments. PLoS ONE |
author_facet |
Robert Theodor Mallmann Claudio Elgueta Faten Sleman Jan Castonguay Thomas Wilmes Arn van den Maagdenberg Norbert Klugbauer |
author_sort |
Robert Theodor Mallmann |
title |
Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments. |
title_short |
Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments. |
title_full |
Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments. |
title_fullStr |
Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments. |
title_full_unstemmed |
Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments. |
title_sort |
ablation of ca(v)2.1 voltage-gated ca²⁺ channels in mouse forebrain generates multiple cognitive impairments. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Voltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V)2.1 mouse models. Global Ca(V)2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V)2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V)2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V)2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V)2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V)2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V)2.1 in the adult murine forebrain. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24205277/pdf/?tool=EBI |
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