Increased network excitability and impaired induction of long-term potentiation in the dentate gyrus of collybistin-deficient mice in vivo

被引:47
作者
Jedlicka, Peter [1 ,2 ]
Papadopoulos, Theofilos [2 ]
Deller, Thomas [1 ]
Betz, Heinrich [2 ]
Schwarzacher, Stephan W. [1 ]
机构
[1] Univ Frankfurt, Inst Clin Neuroanat, D-60590 Frankfurt, Germany
[2] Max Planck Inst Brain Res, Dept Neurochem, D-60528 Frankfurt, Germany
关键词
GABA(A) receptor; Gephyrin; GEF; Synaptic plasticity; Granule cell; GABA(A) RECEPTOR SUBTYPES; EXCHANGE FACTOR COLLYBISTIN; PERISOMATIC INHIBITION; GABAERGIC SYNAPSES; SYNAPTIC PLASTICITY; MENTAL-RETARDATION; GEPHYRIN; HIPPOCAMPUS; RAT; MODEL;
D O I
10.1016/j.mcn.2009.02.005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Collybistin (Cb), a brain-specific guanine nucleotide exchange factor, has been shown to be essential for the gephyrin-dependent clustering of a specific set of GABA(A) receptors at inhibitory postsynaptic sites. Here, we examined whether the lack of Cb affects synaptic properties and neuronal activity in the intact hippocampus by monitoring network activity in the dentate gyrus of Cb-deficient mice after perforant-path stimulation in vivo. We found a decreased threshold for evoked population spikes of granule cells, indicating their increased excitability. Paired-pulse inhibition of the population spike, a measure for somatic GABAergic network inhibition, was enhanced. Mutant mice exhibited steeper slopes of field excitatory postsynaptic potentials, consistent with a reduced dendritic inhibition, In addition, the induction of long-term potentiation (LTP) was reduced. In line with these functional changes, the number of postsynaptic gephyrin and GABA(A) receptor clusters in the Cb-deficient dentate gyrus was significantly decreased. In conclusion, our data provide the first evidence that Cb-deficiency leads to significant changes of GABAergic inhibition, network excitability and synaptic plasticity in vivo. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:94 / 100
页数:7
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