Roles of endocannabinoids in heterosynaptic long-term depression of excitatory synaptic transmission in visual cortex of young mice
Roles of endocannabinoids in heterosynaptic long-term depression of excitatory synaptic transmission in visual cortex of young mice
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DOI：
10.1523/jneurosci.0899-08.2008
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发表时间：
2008-07-09
影响因子：
5.3
通讯作者：
Tsumoto, Tadaharu
中科院分区：
文献类型：
--
作者：
Huang, Yan;Yasuda, Hiroki;Tsumoto, Tadaharu
在一定条件下，对会聚到视皮层神经元的两条传入通路之一的强直刺激可诱导另一条非激活通路的突触传递的长时程抑制（LTD）。这种形式的突触可塑性称为heterosynaptic LTD（hetero-LTD）在以前的研究中没有系统地研究，而homosynaptic LTD已被广泛研究。为了确定是否异LTD是诱导小鼠的视觉皮层切片，如果是这样，通过什么机制，我们记录EPSPs诱发层II/III神经元交替测试刺激的两个网站在层IV在0.05 Hz。θ爆发刺激一个部位后，在大多数神经元中，由另一个部位的测试刺激诱发的EPSP被长时间抑制，而在激活的突触处诱导同突触长时程增强。这种异源LTD在大多数小鼠中在出生后第7-20天（P7-P20）被诱导，但在小鼠中在P35-P41未被诱导。使用成对脉冲刺激协议和变异系数分析的测试表明，异LTD在突触前位点表达。药理学分析表明，这种形式的LTD是通过激活5型代谢型谷氨酸受体诱导的，而不是通过NMDA型谷氨酸受体。使用大麻素1型受体激动剂和拮抗剂的其他分析表明，内源性大麻素（eCBs）参与这种类型的LTD。此外，结果表明，脑源性神经营养因子，这可能是从强烈激活的突触前位点释放，防止eCBs抑制释放这些网站的递质。
Tetanic stimulation of one of two afferent pathways converging to neurons in the visual cortex induces long-term depression (LTD) of synaptic transmission in the other, nonactivated pathway under a certain condition. This form of synaptic plasticity called heterosynaptic LTD (hetero-LTD) was not systematically investigated in previous studies, whereas homosynaptic LTD has been extensively studied. To determine whether hetero-LTD is induced in visual cortical slices of mice and, if so, through what mechanisms, we recorded EPSPs evoked in layer II/III neurons by alternating test stimulation of two sites in layer IV at 0.05 Hz. After theta-burst stimulation of one site, EPSPs evoked by test stimulation of the other site were depressed for a long time in most of the neurons, whereas homosynaptic long-term potentiation was induced at activated synapses. Such a hetero-LTD was induced in most mice at postnatal day 7-20 (P7-P20), but not induced in mice at P35-P41. Tests using the paired-pulse stimulation protocol and coefficient of variation analysis suggested that hetero-LTD was expressed at presynaptic sites. Pharmacological analysis indicated that this form of LTD was induced through activation of the type 5 of metabotropic glutamate receptors, not through the NMDA type of glutamate receptors. Additional analysis using a cannabinoid type 1 receptor agonist and an antagonist suggested that endocannabinoids (eCBs) are involved in this type of LTD. Moreover, results suggest that brain-derived neurotrophic factor, which may be released from strongly activated presynaptic sites, prevents eCBs from suppressing the release of transmitters from these sites.