Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor.
Hyperexcitability in combined entorhinal/hippocampal slices of adult rat after exposure to brain-derived neurotrophic factor.
复制标题
DOI：
10.1152/jn.1997.78.2.1082
复制
发表时间：
1997-08
影响因子：
2.5
通讯作者：
H. Scharfman
中科院分区：
文献类型：
--
作者：
H. Scharfman
脑片上应用脑源性神经营养因子(BDNF)浸浴，观察脑片CA3区、齿状回和内侧内嗅皮质脑源性神经营养因子的电生理作用。在大多数脑片上，用25-100 ng/mlBDNF浸浴30-90分钟，可增强对选择性通路中单一传入刺激的反应。在CA3区，73%的脑片对苔藓纤维刺激的反应增强，而内嗅皮层对白质刺激的反应在脑片中增加。在暴露于脑源性神经营养因子后，这些区域也表现出过度兴奋的证据，因为对重复刺激(1赫兹成对脉冲，几个S)的反应产生了多个群体棘波，以回应对CA3区苔藓纤维刺激的反应，或对内嗅皮层白质刺激的多场电位的反应。重复刺激结束后，重复场电位持续存在，通常伴随着扩散性抑制。在未经处理的脑片或应用煮沸的BDNF或细胞色素C后，从未出现对单一刺激的反应增强和超兴奋性。酪氨酸激酶拮抗剂K252a(2微米)阻断了BDNF的作用。在CA3区，由于刺激苔藓纤维的反应受到影响，而对海马伞或Schaffer侧支刺激的反应不受影响，因此对单一刺激的反应增强和超兴奋性都表现出传入的特异性。此外，齿状回受到的影响要小得多，这也证明了区域特异性。脑源性神经营养因子在CA3区的作用与小剂量海人酸浴产生的作用相似，海人酸被认为是通过突触前作用来调节苔藓纤维终末的谷氨酸释放。这些结果表明，BDNF对海马-内嗅觉回路不同区域的兴奋性有急性影响。这些影响似乎在BDNF高度免疫反应的区域最大，例如苔藓纤维和内嗅皮层。尽管本实验没有明确的机制(S)，但传入的特异性、与红藻氨酸的作用相似以及被K252a阻断与以前的假说是一致的，即脑源性神经营养因子通过突触前作用于调节兴奋性氨基酸传递的TrkB受体而影响急性兴奋性。然而，我们不能排除对抑制性突触或突触后过程的作用。
Effects of brain-derived neurotrophic factor (BDNF) in area CA3, the dentate gyrus, and medial entorhinal cortex were examined electrophysiologically by bath application of BDNF in slices containing the hippocampus and entorhinal cortex. Bath application of 25-100 ng/ml BDNF for 30-90 min increased responses to single afferent stimuli in selective pathways in the majority of slices. In area CA3, responses to mossy fiber stimulation increased in 73% of slices and entorhinal cortex responses to white matter stimulation increased in 64% of slices. After exposure to BDNF, these areas also demonstrated evidence of hyperexcitability, because responses to repetitive stimulation (1-Hz paired pulses for several s) produced multiple population spikes in response to mossy fiber stimulation in CA3 or multiple field potentials in response to white matter stimulation in the entorhinal cortex. Repetitive field potentials persisted after repetitive stimulation ended and usually were followed by spreading depression. Enhancement of responses to single stimuli and hyperexcitability were never evoked in untreated slices or after bath application of boiled BDNF or cytochrome C. The tyrosine kinase antagonist K252a (2 microM) blocked the effects of BDNF. In area CA3, both the potentiation of responses to single stimuli and hyperexcitability showed afferent specificity, because responses to mossy fiber stimulation were affected but responses to fimbria or Schaffer collateral stimulation were not. In addition, regional specificity was demonstrated in that the dentate gyrus was much less affected. The effects of BDNF in area CA3 were similar to those produced by bath application of low doses of kainic acid, which is thought to modulate glutamate release from mossy fiber terminals by a presynaptic action. These results suggest that BDNF has acute effects on excitability in different areas of the hippocampal-entorhinal circuit. These effects appear to be greatest in areas that are highly immunoreactive for BDNF, such as the mossy fibers and the entorhinal cortex. Although the present experiments do not elucidate mechanism(s) definitively, the afferent specificity, similarity to the effects of kainic acid, and block by K252a are consistent with previous hypotheses that BDNF affects acute excitability by a presynaptic action on trkB receptors that modulate excitatory amino acid transmission. However, we cannot rule out actions on inhibitory synapses or postsynaptic processes.