Massey Kerri A, Zago Wagner M, Berg Darwin K
Neurobiology Section, Division of Biological Sciences, 0357, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0357, USA.
Mol Cell Neurosci. 2006 Dec;33(4):381-8. doi: 10.1016/j.mcn.2006.08.011. Epub 2006 Oct 9.
In the hippocampus, brain-derived neurotrophic factor (BDNF) regulates a number of synaptic components. Among these are nicotinic acetylcholine receptors containing alpha7 subunits (alpha7-nAChRs), which are interesting because of their relative abundance in the hippocampus and their high relative calcium permeability. We show here that BDNF elevates surface and intracellular pools of alpha7-nAChRs on cultured hippocampal neurons and that glutamatergic activity is both necessary and sufficient for the effect. Blocking transmission through NMDA receptors with APV blocked the BDNF effect; increasing spontaneous excitatory activity with the GABA(A) receptor antagonist bicuculline replicated the BDNF effect. BDNF antibodies blocked the BDNF-mediated increase but not the bicuculline one, consistent with enhanced glutamatergic activity acting downstream from BDNF. Increased alpha7-nAChR clusters were most prominent on interneuron subtypes known to directly innervate excitatory neurons. The results suggest that BDNF, acting through glutamatergic transmission, can modulate hippocampal output in part by controlling alpha7-nAChR levels.
在海马体中，脑源性神经营养因子（BDNF）调节多种突触成分。其中包括含有α7亚基的烟碱型乙酰胆碱受体（α7-nAChRs），因其在海马体中相对丰富且相对钙通透性高而备受关注。我们在此表明，BDNF可提高培养的海马神经元上α7-nAChRs的表面池和细胞内池水平，且谷氨酸能活性对于该效应既是必需的也是充分的。用APV阻断通过NMDA受体的传递可阻断BDNF的作用；用GABA(A)受体拮抗剂荷包牡丹碱增加自发兴奋性活动可复制BDNF的作用。BDNF抗体可阻断BDNF介导的增加，但不能阻断荷包牡丹碱介导的增加，这与BDNF下游谷氨酸能活性增强一致。增加的α7-nAChR簇在已知直接支配兴奋性神经元的中间神经元亚型上最为突出。结果表明，BDNF通过谷氨酸能传递发挥作用，可部分通过控制α7-nAChR水平来调节海马体输出。
