Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons
Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons
复制标题
DOI：
10.1152/jn.2000.83.6.3287
复制
发表时间：
2000-06-01
影响因子：
2.5
通讯作者：
Crepel, F
中科院分区：
文献类型：
--
作者：
Auclair, N;Otani, S;Crepel, F
据报道，大麻素受体在CNS的许多结构中调节突触传递，但对它们在表达I型大麻素受体（CB-1）的前额叶皮层中的作用知之甚少。在本研究中，我们首先检测了CB-1的选择性激动剂和拮抗剂对大鼠前额叶皮层脑片兴奋性突触后电流（EPSC）的急性作用。刺激V层传入神经可在膜片钳V层锥体细胞中诱发EPSC。单突触EPSC被大麻素受体激动剂WIN 55212 -2（-50.4 +/-8.8%）和CP 55940（-42.4 +/-10.9%）的浴应用（1 μ M）强烈抑制。CB-1拮抗剂SR 141716 A逆转了这些作用。出乎意料的是，单独使用SR 141716 A可显著增加突触能传递（+46.9 +/-11.2%），这可被WIN 55212 -2部分逆转。在浴中存在锶的情况下，通过刺激V层传入在V层锥体细胞中诱发的异步突触事件的频率而不是振幅显著降低（-54.2 +/-8%），表明大麻素在这些突触处的突触前作用部位。强直刺激（100 Hz，4串，100脉冲）在控制条件下诱导，无变化（n = 7/18），长时程抑制（LTD; n = 6/18），或长时程增强（LTP; n = 5/18）的单突触EPSC刺激V层传入诱发。当在浴中存在WIN 55，212 -2或SR 141716-A（1 mM）的情况下应用破伤风时，“非可塑性”细胞的比例没有显著变化（两种情况下n = 7/15）。对于塑料（两种情况下n = 8），WIN 55，212 -2强烈支持LTD（n = 7/8），明显损害LTP（n = 1/8），而SR 141716-A观察到相反的效果（7/8 LTP; 1/8 LTD）。这些结果表明，大麻素影响啮齿动物PFC的神经元能突触传递和可塑性。
Cannabinoids receptors have been reported to modulate synaptic transmission in many structures of the CNS, but yet little is known about their role in the prefrontal cortex where type I cannabinoid receptor (CB-1) are expressed. In this study, we tested first the acute effects of selective agonists and antagonist of CB-1 on glutamatergic excitatory postsynaptic currents (EPSCs) in slices of rat prefrontal cortex (PFC). EPSCs were evoked in patch-clamped layer V pyramidal cells by stimulation of layer V afferents. Monosynaptic EPSCs were strongly depressed by bath application (1 mu M) of the cannabinoid receptors agonists WIN55212-2 (-50.4 +/- 8.8%) and CP55940 (-42.4 +/- 10.9%). The CB-1 antagonist SR141716A reversed these effects. Unexpectedly, SR141716A alone produced a significant increase of glutamatergic synaptic transmission (+46.9 +/- 11.2%), which could be partly reversed by WIN55212-2. In the presence of strontium in the bath, the frequency but not the amplitude of asynchronous synaptic events evoked in layer V pyramidal cells by stimulating layer V afferents, was markedly decreased (-54.2 +/- 8%), indicating a presynaptic site of action of cannabinoids at these synapses. Tetanic stimulation (100 pulses at 100 Hz, 4 trains) induced in control condition, no changes (n = 7/18), long-term depression (LTD; n = 6/18), or long-term potentiation (LTP; n = 5/18) of monosynaptic EPSCs evoked by stimulation of layer V afferents. When tetanus was applied in the presence of WIN 55,212-2 or SR141716-A (1 mM) in the bath, the proportion of "nonplastic" cells were not significantly changed (n = 7/15 in both cases). For the plastic ones (n = 8 in both cases), WIN 55,212-2 strongly favored LTD (n = 7/8) at the apparent expense of LTP (n = 1/8), whereas the opposite effect was observed with SR141716-A (7/8 LTP; 1/8 LTD). These results demonstrate that cannabinoids influence glutamatergic synaptic transmission and plasticity in the PFC of rodent.