雖然突觸粘附蛋白已被識別為精神分裂癥的遺傳風險因子，但尚不清楚它們在病情發(fā)展中扮演什么角色,。一項新的研究表明,，Neuregulin-1 (Nrg1) 及其受體 ErbB4的功能是調(diào)控特定抑制性皮層回路中的連接性。
由于人們對抑制性突觸是怎樣形成的知之甚少,，所以這項研究為Nrg1/ErbB4信號作用在這一過程中的參與提供了重要證據(jù),，并且還為了解這些基因在精神分裂癥的發(fā)病中所起作用提供了一個視角。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature doi:10.1038/nature08928
Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling
Pietro Fazzari,Ana V. Paternain,Manuel Valiente,Ramón Pla,Rafael Luján,Kent Lloyd,Juan Lerma,Oscar Marín& Beatriz Rico
Schizophrenia is a complex disorder that interferes with the function of several brain systems required for cognition and normal social behaviour. Although the most notable clinical aspects of the disease only become apparent during late adolescence or early adulthood, many lines of evidence suggest that schizophrenia is a neurodevelopmental disorder with a strong genetic component1, 2. Several independent studies have identified neuregulin 1 (NRG1) and its receptor ERBB4 as important risk genes for schizophrenia3, 4, although their precise role in the disease process remains unknown. Here we show that Nrg1 and ErbB4 signalling controls the development of inhibitory circuitries in the mammalian cerebral cortex by cell-autonomously regulating the connectivity of specific GABA (γ-aminobutyric acid)-containing interneurons. In contrast to the prevalent view, which supports a role for these genes in the formation and function of excitatory synapses between pyramidal cells, we found that ErbB4 expression in the mouse neocortex and hippocampus is largely confined to certain classes of interneurons. In particular, ErbB4 is expressed by many parvalbumin-expressing chandelier and basket cells, where it localizes to axon terminals and postsynaptic densities receiving glutamatergic input. Gain- and loss-of-function experiments, both in vitro and in vivo, demonstrate that ErbB4 cell-autonomously promotes the formation of axo-axonic inhibitory synapses over pyramidal cells, and that this function is probably mediated by Nrg1. In addition, ErbB4 expression in GABA-containing interneurons regulates the formation of excitatory synapses onto the dendrites of these cells. By contrast, ErbB4 is dispensable for excitatory transmission between pyramidal neurons. Altogether, our results indicate that Nrg1 and ErbB4 signalling is required for the wiring of GABA-mediated circuits in the postnatal cortex, providing a new perspective to the involvement of these genes in the aetiology of schizophrenia.
