کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4322577 1291718 2007 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity
چکیده انگلیسی

SummaryNeuregulin-1 (NRG1) signaling participates in numerous neurodevelopmental processes. Through linkage analysis, nrg1 has been associated with schizophrenia, although its pathophysiological role is not understood. The prevailing models of schizophrenia invoke hypofunction of the glutamatergic synapse and defects in early development of hippocampal-cortical circuitry. Here, we show that the erbB4 receptor, as a postsynaptic target of NRG1, plays a key role in activity-dependent maturation and plasticity of excitatory synaptic structure and function. Synaptic activity leads to the activation and recruitment of erbB4 into the synapse. Overexpressed erbB4 selectively enhances AMPA synaptic currents and increases dendritic spine size. Preventing NRG1/erbB4 signaling destabilizes synaptic AMPA receptors and leads to loss of synaptic NMDA currents and spines. Our results indicate that normal activity-driven glutamatergic synapse development is impaired by genetic deficits in NRG1/erbB4 signaling leading to glutamatergic hypofunction. These findings link proposed effectors in schizophrenia: NRG1/erbB4 signaling perturbation, neurodevelopmental deficit, and glutamatergic hypofunction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 54, Issue 4, 24 May 2007, Pages 583–597
نویسندگان
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