کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6022226 | 1580666 | 2013 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin-Lowry syndrome
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کلمات کلیدی
MPPCLSIEGmGluRGluRNMDARfEPSPMSBITIRSKMedial perforant pathCoffin–Lowry syndromeAMPARPTPPPFCREBPSDPPIMSK1/2ERKEPSC - EPSCoRSTP - PTSα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor - α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptorISI - آی اس آیReconsolidation - بازسازیpostsynaptic density - تراکم Postinapticpaired-pulse facilitation - تسکین زوایای پالسیlong-term potentiation - تقویت درازمدتLTP - تقویت طولانی مدت یا LTP excitatory postsynaptic currents - جریان های پسینپتیک هیجان انگیزtrace fear conditioning - ردیابی تهدید ترسTranscription factors - عوامل رونویسیinter-trial interval - فاصله بین محاکمهinter-stimulus interval - فاصله بین محرکunconditioned stimulus - محرک بی قید و شرطconditioned stimulus - محرک شرطیPaired-pulse inhibition - مهار زوج پالسSynaptic morphology - مورفولوژی سیناپتیکElectron microscopy - میکروسکوپ الکترونیintellectual disability - ناتوانی ذهنیwild-type - نوع وحشیHippocampus - هیپوکامپ Post-tetanic potentiation - پتانسیل پست تکتانیکField excitatory postsynaptic potential - پتانسیل پستنیپتیک مزمن تحریک پذیرShort-term potentiation - پتانسیل کوتاه مدتcAMP-response element binding protein - پروتئین اتصال دهنده عنصر cAMPSynaptic plasticity - پلاستیسیته سیناپسیimmediate early gene - ژن فوری اولیهMental retardation - کمتوانی ذهنیextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیN-methyl-d-aspartate receptor - گیرنده N-methyl-d-aspartateMetabotropic glutamate receptor - گیرنده گلوتامات متابوتروپیکGlutamate receptor - گیرنده گلومات
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The Coffin-Lowry syndrome (CLS) is a syndromic form of intellectual disability caused by loss-of-function of the RSK2 serine/threonine kinase encoded by the rsk2 gene. Rsk2 knockout mice, a murine model of CLS, exhibit spatial learning and memory impairments, yet the underlying neural mechanisms are unknown. In the current study, we examined the performance of Rsk2 knockout mice in cued, trace and contextual fear memory paradigms and identified selective deficits in the consolidation and reconsolidation of hippocampal-dependent fear memories as task difficulty and hippocampal demand increase. Electrophysiological, biochemical and electron microscopy analyses were carried out in the dentate gyrus of the hippocampus to explore potential alterations in neuronal functions and structure. In vivo and in vitro electrophysiology revealed impaired synaptic transmission, decreased network excitability and reduced AMPA and NMDA conductance in Rsk2 knockout mice. In the absence of RSK2, standard measures of short-term and long-term potentiation (LTP) were normal, however LTP-induced CREB phosphorylation and expression of the transcription factors EGR1/ZIF268 were reduced and that of the scaffolding protein SHANK3 was blocked, indicating impaired activity-dependent gene regulation. At the structural level, the density of perforated and non-perforated synapses and of multiple spine boutons was not altered, however, a clear enlargement of spine neck width and post-synaptic densities indicates altered synapse ultrastructure. These findings show that RSK2 loss-of-function is associated in the dentate gyrus with multi-level alterations that encompass modifications of glutamate receptor channel properties, synaptic transmission, plasticity-associated gene expression and spine morphology, providing novel insights into the mechanisms contributing to cognitive impairments in CLS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 58, October 2013, Pages 156-168
Journal: Neurobiology of Disease - Volume 58, October 2013, Pages 156-168
نویسندگان
Elise Morice, Séverine Farley, Roseline Poirier, Glenn Dallerac, Carine Chagneau, Solange Pannetier, André Hanauer, Sabrina Davis, Cyrille Vaillend, Serge Laroche,