Abstract：
:Using the rat model of early life seizures (ELS), which has exaggerated mGluR mediated long-term depression of synaptic strength (mGluR-LTD) in adulthood, we probed the signaling cascades underlying mGluR-LTD induction. Several inhibitors completely blocked mGluR-LTD in control but not in ELS rats: the proteasome, the mammalian target of rapamycin (mTOR), S6 kinase (S6K), or L-type voltage-gated calcium channels (L-type VGCC). Inhibition of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) resulted in a near complete block of mGluR-LTD in control rats and a slight reduction of mGluR-LTD in ELS rats. "Autonomous" CaMKII was found to be upregulated in ELS rats, while elevated S6K activity, which is stimulated by mTOR, was described previously. Thus, modulation of each of these factors was necessary for mGluR-LTD induction in control rats, but even their combined, permanent activation in the ELS rats was not sufficient to individually support mGluR-LTD induction following ELS. This implies that while these factors may act sequentially in controls to mediate mGluR-LTD, this is no longer the case after ELS. In contrast, activated ERK was found to be significantly down-regulated in ELS rats. Inhibition of MEK/ERK activation in control rats elevated mGluR-LTD to the exaggerated levels seen in ELS rats. Together, these results elucidate both the mechanisms that persistently enhance mGluR-LTD after ELS and the mechanisms underlying normal mGluR-LTD by providing evidence for multiple, convergent pathways that mediate mGluR-LTD induction. With our prior work, this ties these signaling cascades to the ELS behavioral phenotype that includes abnormal working memory, fear conditioning and socialization.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Bernard PB,Castano AM,Bayer KU,Benke TAdoi
10.1016/j.neuropharm.2014.04.011subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1-12eissn
0028-3908issn
1873-7064pii
S0028-3908(14)00137-3journal_volume
84pub_type
杂志文章abstract：:The guinea-pig substantia nigra receives a 5-hydroxytryptaminergic (5-HT ergic) projection from the dorsal raphé nucleus. In this study we have attempted to identify the 5-HT receptor subtype mediating release of acetylcholinesterase (AChE) from nigral neurones, measured by assay of perfusate obtained via chronically ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00088-n
更新日期：1995-09-01 00:00:00
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journal_title：Neuropharmacology
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更新日期：2015-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：1996-02-01 00:00:00
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更新日期：1993-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.004
更新日期：2017-01-01 00:00:00
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更新日期：2016-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90260-1
更新日期：1986-03-01 00:00:00
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journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2010.02.018
更新日期：2010-06-01 00:00:00
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journal_title：Neuropharmacology
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更新日期：2019-05-15 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：1982-07-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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更新日期：2016-07-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.12.013
更新日期：2019-04-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.05.034
更新日期：2013-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90170-4
更新日期：1985-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.08.022
更新日期：2013-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.07.035
更新日期：2017-02-01 00:00:00
abstract：:A cDNA encoding the human metabotropic glutamate receptor type 4 (hmGluR4) was isolated from human brain cDNA libraries by cross-hybridization with rat mGluR4 probes. The deduced amino acid sequence of human mGluR4 consists of 912 residues and shows a sequence identity of 96% to the amino acid sequence of rat mGluR4. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)00149-m
更新日期：1995-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2004-03-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.09.002
更新日期：2016-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.07.035
更新日期：2004-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90105-3
更新日期：1983-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2015-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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更新日期：2020-05-15 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90183-8
更新日期：1986-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90161-3
更新日期：1985-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2018-09-15 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90071-i
更新日期：1991-06-01 00:00:00
abstract：:LY354740 is a potent and selective mGlu2/3 receptor agonist with activity in models of psychiatric disorders (anxiety, psychosis), and early clinical studies in anxiety patients. However, the specific receptor subtypes and brain regions which mediate mGlu2/3 receptor agonist pharmacology/efficacy are not well understo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.03.014
更新日期：2006-08-01 00:00:00
abstract：:γ-Aminobutyric acid type A receptors that contain the δ subunit (δGABAA receptors) are expressed in multiple types of neurons throughout the central nervous system, where they generate a tonic conductance that shapes neuronal excitability and synaptic plasticity. These receptors regulate a variety of important behavio...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2014.08.003
更新日期：2015-01-01 00:00:00
