Brumwell Craig L, Johnson James L, Jacob Michele H
Department of Neuroscience, Tufts University, Sackler School of Biomedical Sciences, Boston, Massachusetts 02111, USA.
J Neurosci. 2002 Sep 15;22(18):8101-9. doi: 10.1523/JNEUROSCI.22-18-08101.2002.
Alpha7-nicotinic acetylcholine receptors (nAChRs) are widely expressed in the vertebrate nervous system. alpha7-nAChR functions include postsynaptic transmission, modulating neurotransmitter release, reinforcing nicotine addiction, and a role in neurological disorders, such as schizophrenia and Alzheimer's disease. In chick parasympathetic ciliary ganglion (CG) neurons, alpha7-nAChRs are excluded from the synapse and localize perisynaptically. Despite their extrasynaptic distribution, the highly Ca2+-permeable alpha7-nAChRs have important synapse-related Ca2+-dependent signaling functions in the CG. We show here that the synaptic partners regulate alpha7-nAChR expression during synapse formation in embryonic CG neurons in situ. The absence of inputs and target tissues cause reductions in alpha7-nAChR mRNA and protein levels that primarily resemble those seen for synaptic alpha3-nAChRs. However, there is a difference in their regulation. alpha7-nAChR levels are downregulated by reduced activity, whereas alpha3-nAChR levels are not. We propose that the activity-dependent regulation of extrasynaptic alpha7-nAChR levels may be an important mechanism for postsynaptic CG neurons to detect changes in presynaptic activity levels and respond with Ca2+-dependent plasticity changes in gene expression.
α7-烟碱型乙酰胆碱受体（nAChRs）在脊椎动物神经系统中广泛表达。α7-nAChR的功能包括突触后传递、调节神经递质释放、强化尼古丁成瘾以及在神经疾病（如精神分裂症和阿尔茨海默病）中发挥作用。在鸡的副交感睫状神经节（CG）神经元中，α7-nAChRs被排除在突触之外，定位于突触周围。尽管它们分布在突触外，但高度Ca2+通透的α7-nAChRs在CG中具有重要的与突触相关的Ca2+依赖性信号传导功能。我们在此表明，突触伙伴在胚胎CG神经元原位突触形成过程中调节α7-nAChR的表达。输入和靶组织的缺失会导致α7-nAChR mRNA和蛋白水平降低，这主要类似于突触α3-nAChRs的情况。然而，它们的调节存在差异。α7-nAChR水平因活性降低而下调，而α3-nAChR水平则不然。我们提出，突触外α7-nAChR水平的活性依赖性调节可能是突触后CG神经元检测突触前活性水平变化并以基因表达中Ca2+依赖性可塑性变化做出反应的重要机制。
