2017
DOI: 10.1523/jneurosci.0539-17.2017
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Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice

Abstract: Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal… Show more

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Cited by 78 publications
(112 citation statements)
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“…Despite its role in cytoskeletal and cargo transport regulation, we did not find major differences in dendrite morphologies of CDKL5 KO mice in culture or in vivo . Our results are in agreement with reports where subtle reductions in dendrite length were observed in CDLK5‐deficient pyramidal neurons from CDKL5 KO mice (Tang et al , ; Zhou et al , ), but contrast with major dendritic alterations (Amendola et al , ). Modest reductions in dendrite arborization could be caused by compromised anterograde trafficking in CDKL5 KO dendrites.…”
Section: Discussionsupporting
confidence: 93%
“…Despite its role in cytoskeletal and cargo transport regulation, we did not find major differences in dendrite morphologies of CDKL5 KO mice in culture or in vivo . Our results are in agreement with reports where subtle reductions in dendrite length were observed in CDLK5‐deficient pyramidal neurons from CDKL5 KO mice (Tang et al , ; Zhou et al , ), but contrast with major dendritic alterations (Amendola et al , ). Modest reductions in dendrite arborization could be caused by compromised anterograde trafficking in CDKL5 KO dendrites.…”
Section: Discussionsupporting
confidence: 93%
“…However, in conditional knockout mice in which CDKL5 was ablated specifically from forebrain excitatory neurons, a trend toward an increase in spine density and volume was observed (Tang et al, 2017). In support of this morphological change, the frequency of spontaneous miniature EPSC was increased (Tang et al, 2017). The cause of this discrepancy is not clear.…”
Section: Role Of Cdkl5 In Synapse Formationmentioning
confidence: 99%
“…In one line, the total length of apical dendrites was significantly reduced in cortical and hippocampal CA1 pyramidal neurons , and in dentate gyrus granule cells Fuchs et al, 2015). In another mouse line, the dendritic complexity of CA1 pyramidal neurons was decreased although the total length was not significantly changed (Tang et al, 2017). Importantly, CDKL5 is not only required, but sufficient to promote dendrite growth.…”
Section: Cdkl5 Regulates Dendrite Developmentmentioning
confidence: 99%
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