ErbB4是成年海马体中长时程增强的抑制因子。
ErbB4 is a suppressor of long-term potentiation in the adult hippocampus.
作者信息
Pitcher Graham M, Beggs Simon, Woo Ran-Sook, Mei Lin, Salter Michael W
机构信息
Program in Neurosciences & Mental Health, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
出版信息
Neuroreport. 2008 Jan 22;19(2):139-43. doi: 10.1097/WNR.0b013e3282f3da10.
Abstract
ErbB4 has emerged as a leading susceptibility gene for schizophrenia but the function of the ErbB4 receptor in the adult brain is unknown. Here, we show in the adult hippocampus that long-term potentiation (LTP) of transmission at Schaffer collateral CA1 synapses was markedly enhanced in mutant mice lacking ErbB4. Concordantly, LTP was enhanced by acutely blocking ErbB4 in wild-type animals, indicating that ErbB4 activity constitutively suppresses LTP. Moreover, increasing ErbB4 signaling further suppressed LTP. By contrast, altering ErbB4 activity did not affect basal synaptic transmission or short-term facilitation. Our findings suggest that cognitive deficits in schizophrenia may be a consequence of hyperfunction of ErbB4 signaling leading to suppressed glutamatergic synaptic plasticity, thus opening new approaches for the treatment of this disorder.
摘要
ErbB4已成为精神分裂症的一个主要易感基因，但ErbB4受体在成人大脑中的功能尚不清楚。在此，我们在成年海马体中发现，在缺乏ErbB4的突变小鼠中，Schaffer侧支CA1突触传递的长时程增强（LTP）显著增强。与此一致的是，在野生型动物中急性阻断ErbB4可增强LTP，这表明ErbB4活性可组成性地抑制LTP。此外，增加ErbB4信号传导会进一步抑制LTP。相比之下，改变ErbB4活性并不影响基础突触传递或短期易化。我们的研究结果表明，精神分裂症中的认知缺陷可能是ErbB4信号传导功能亢进导致谷氨酸能突触可塑性受抑制的结果，从而为治疗这种疾病开辟了新途径。
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