BDNF-induced endocannabinoid release modulates neocortical glutamatergic neurotransmission.
BDNF-induced endocannabinoid release modulates neocortical glutamatergic neurotransmission.
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DOI：
10.1002/syn.21962
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Levine ES
中科院分区：
文献类型：
--
作者：
Yeh ML;Selvam R;Levine ES
内源性大麻素（eCB）和神经营养因子，特别是脑源性神经营养因子（BDNF），是在整个哺乳动物新皮层中发现的有效神经调质。eCB和BDNF在许多行为和神经生理过程中起着关键作用，并且是开发新疗法的目标。eCB和BDNF的作用主要分别由1型大麻素（CB 1）受体和trkB酪氨酸激酶受体介导。我们的实验室和其他实验室先前已经确定BDNF通过增强突触前谷氨酸释放和调节NMDA受体来增强兴奋性传递。相反，我们已经表明，BDNF通过诱导eCB的突触后释放来减弱抑制性传递，所述eCB逆行地作用以抑制躯体感觉皮层的第2/3层中的GABA释放。在这里，我们假设BDNF也诱导兴奋性突触释放eCB，这可能对BDNF的直接突触前效应有缓解或相反的作用。我们发现CB 1和trkB和受体的表达水平最高的层2/3和5。令人惊讶的是，BDNF并没有增加自发的微型兴奋性突触后电流（mEPSC）的频率到层5锥体神经元的躯体感觉皮层，在海马和视觉皮层的效果相反。然而，BDNF对体感皮层mEPSC频率的影响通过阻断CB 1受体或破坏eCB释放而被揭示。因此，BDNF-trKB信号通过相反的作用调节体感皮层中的谷氨酸释放，直接突触前增强释放概率，同时突触后诱导的eCB释放通过突触前CB 1受体降低释放概率。
Endocannabinoids (eCBs) and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), are potent neuromodulators found throughout the mammalian neocortex. Both eCBs and BDNF play critical roles in many behavioral and neurophysiological processes and are targets for the development of novel therapeutics. The effects of eCBs and BDNF are primarily mediated by the type 1 cannabinoid (CB1) receptor and the trkB tyrosine kinase receptor, respectively. Our laboratory and others have previously established that BDNF potentiates excitatory transmission by enhancing presynaptic glutamate release and modulating NMDA receptors. In contrast, we have shown that BDNF attenuates inhibitory transmission by inducing postsynaptic release of eCBs that act retrogradely to suppress GABA release in layer 2/3 of somatosensory cortex. Here, we hypothesized that BDNF also induces release of eCBs at excitatory synapses, which could have a mitigating or opposing effect on the direct presynaptic effects of BDNF. We found the highest levels of expression of CB1 and trkB and receptors in layers 2/3 and 5. Surprisingly, BDNF did not increase the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs) onto layer 5 pyramidal neurons in somatosensory cortex, in contrast to its effects in the hippocampus and visual cortex. However, the effect of BDNF on mEPSC frequency in somatosensory cortex was unmasked by blocking CB1 receptors or disrupting eCB release. Thus, BDNF-trKB signaling regulates glutamate release in the somatosensory cortex via opposing effects, a direct presynaptic enhancement of release probability, and simultaneous postsynaptically-induced eCB release that decreases release probability via presynaptic CB1 receptors.
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影响因子：
4.7
作者：
Hillard, CJ;Edgemond, WS;Campbell, WB
通讯作者：
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Littleton, J. Troy
DOI：
10.1073/pnas.0509494102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Berghuis, P;Dobszay, MB;Harkany, T
通讯作者：
Harkany, T