Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation-inducing electrical stimulation patterns

Neurotrophin secretion from hippocampal neurons evoked by long-term-potentiation-inducing electrical stimulation patterns
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DOI:
10.1073/pnas.092129699
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发表时间:
2002-04-30
影响因子:
11.1
通讯作者:
Staiger, V
Staiger, V
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gärtner, AG;Staiger, V

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神经营养蛋白(NIT)脑源性神经营养因子(BDNF)在长时程增强(LTP)的形成中起着重要作用。在这里,我们讨论 BDNF 的这种调节是否需要其持续存在,或者在 LTP 启动的特定时间段内是否需要局部增加 BDNF。通过对海马神经元原代培养物进行电场刺激,我们证明诱导 LTP 的短时高频刺激也会引起 BDNF 的瞬时分泌。相反,低频刺激会诱发长期抑郁,但不会增强 BDNF 分泌,这表明 BDNF 在 LTP 诱导时是特定存在的,因此是必需的。场刺激介导的 BDNF 分泌取决于动作电位的形成,并由 IP3 介导的细胞内 Ca2+ 释放诱导。旨在确定使用 NT6 的 NIT 分泌位点的实验显示,场刺激的表面标记模式与之前高钾显示的表面标记模式相似。
The neurotrophin (NIT) brain-derived neurotrophic factor (BDNF) plays an essential role in the formation of long-term potentiation (LTP). Here, we address whether this modulation by BDNF requires its continuous presence, or whether a local increase in BDNF is necessary during a specific time period of LTP initiation. Using electrical field stimulation of primary cultures of hippocampal neurons, we demonstrate that short high-frequency bursts of stimuli that induce LTP evoke also an instantaneous secretion of BDNF. In contrast, stimuli at low frequencies, inducing long-term depression, do not enhance BDNF secretion, suggesting that BDNF is specifically present, and thus required, at the time of LTP induction. The field-stimulation-mediated BDNF secretion depends on the formation of action potentials and is induced by IP3-mediated Ca2+ release from intracellular stores. Experiments, aimed at determining the sites of NIT secretion that use NT6, showed similar patterns of surface labeling by field stimulation to those shown previously by high potassium.