Scharfman H E
Neurology Research Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw 10993-1195, USA.
J Neurophysiol. 1997 Aug;78(2):1082-95. doi: 10.1152/jn.1997.78.2.1082.
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.
通过在包含海马体和内嗅皮质的脑片中浴加脑源性神经营养因子（BDNF），以电生理学方法研究了BDNF在CA3区、齿状回和内侧内嗅皮质中的作用。在大多数脑片中，浴加25 - 100 ng/ml BDNF 30 - 90分钟可增强选择性通路中对单个传入刺激的反应。在CA3区，73%的脑片中对苔藓纤维刺激的反应增强，在64%的脑片中内嗅皮质对白质刺激的反应增强。暴露于BDNF后，这些区域还表现出兴奋性过高的迹象，因为对重复刺激（1赫兹成对脉冲持续数秒）的反应在CA3区对苔藓纤维刺激产生多个群体峰电位，或在内嗅皮质对白质刺激产生多个场电位。重复刺激结束后，重复的场电位仍持续存在，且通常随后会出现扩散性抑制。在未处理的脑片或浴加煮沸的BDNF或细胞色素C后，从未诱发对单个刺激反应的增强和兴奋性过高。酪氨酸激酶拮抗剂K252a（2 microM）可阻断BDNF的作用。在CA3区，对单个刺激反应的增强和兴奋性过高均表现出传入特异性，因为对苔藓纤维刺激的反应受到影响，但对穹窿或谢弗侧支刺激的反应未受影响。此外，还表现出区域特异性，即齿状回受影响小得多。BDNF在CA3区的作用类似于浴加低剂量 kainic 酸所产生的作用，kainic 酸被认为通过突触前作用调节苔藓纤维终末的谷氨酸释放。这些结果表明，BDNF对海马 - 内嗅回路不同区域的兴奋性有急性作用。这些作用在对BDNF高度免疫反应的区域似乎最大，如苔藓纤维和内嗅皮质。虽然目前的实验未能明确阐明其机制，但传入特异性、与kainic 酸作用的相似性以及被K252a阻断与先前的假设一致，即BDNF通过对调节兴奋性氨基酸传递的trkB受体的突触前作用影响急性兴奋性。然而，我们不能排除其对抑制性突触或突触后过程的作用。
