Abstract：
:Mutations in genes regulating mTOR pathway signaling are now recognized as a significant cause of epilepsy. Interestingly, these mTORopathies are often caused by somatic mutations, affecting variable numbers of neurons. To better understand how this variability affects disease phenotype, we developed a mouse model in which the mTOR pathway inhibitor Pten can be deleted from 0 to 40 % of hippocampal granule cells. In vivo, low numbers of knockout cells caused focal seizures, while higher numbers led to generalized seizures. Generalized seizures coincided with the loss of local circuit interneurons. In hippocampal slices, low knockout cell loads produced abrupt reductions in population spike threshold, while spontaneous excitatory postsynaptic currents and circuit level recurrent activity increased gradually with rising knockout cell load. Findings demonstrate that knockout cells load is a critical variable regulating disease phenotype, progressing from subclinical circuit abnormalities to electrobehavioral seizures with secondary involvement of downstream neuronal populations.
journal_name
Prog Neurobioljournal_title
Progress in neurobiologyauthors
LaSarge CL,Pun RYK,Gu Z,Riccetti MR,Namboodiri DV,Tiwari D,Gross C,Danzer SCdoi
10.1016/j.pneurobio.2020.101974subject
Has Abstractpub_date
2020-12-09 00:00:00pages
101974eissn
0301-0082issn
1873-5118pii
S0301-0082(20)30229-Xpub_type
杂志文章abstract：:As the genetics of neurodegenerative disease become better understood, opportunities for genetic susceptibility testing for at-risk individuals will increase. Such testing raises important ethical and practice issues related to test access, informed consent, risk estimation and communication, return of results, and po...
journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
pub_type： 杂志文章,评审
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journal_title：Progress in neurobiology
pub_type： 杂志文章,评审
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更新日期：2013-04-01 00:00:00
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journal_title：Progress in neurobiology
pub_type： 杂志文章,评审
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journal_title：Progress in neurobiology
pub_type： 历史文章,杂志文章,评审
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更新日期：2006-02-01 00:00:00
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journal_title：Progress in neurobiology
pub_type： 杂志文章,评审
doi：10.1016/j.pneurobio.2007.03.004
更新日期：2007-11-01 00:00:00
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journal_title：Progress in neurobiology
pub_type： 杂志文章,评审
doi：10.1016/j.pneurobio.2018.08.002
更新日期：2018-10-01 00:00:00
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journal_title：Progress in neurobiology
pub_type： 杂志文章,评审
doi：10.1016/j.pneurobio.2012.08.002
更新日期：2012-11-01 00:00:00
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journal_title：Progress in neurobiology
pub_type： 杂志文章
doi：10.1016/j.pneurobio.2020.101770
更新日期：2020-04-01 00:00:00
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journal_title：Progress in neurobiology
pub_type： 杂志文章,评审
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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journal_title：Progress in neurobiology
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abstract：:Studies of neuropeptide and peptide hormone signaling are coming of age in Drosophila due to rapid developments in molecular genetics approaches that overcome the difficulties caused by the small size of the fly. In addition we have genome-wide information on genes involved in peptide signaling, and growing pools of p...
journal_title：Progress in neurobiology
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更新日期：2010-09-01 00:00:00
