Analysis of the effects of cannabinoids on identified synaptic connections in the caudate-putamen by paired recordings in transgenic mice
Analysis of the effects of cannabinoids on identified synaptic connections in the caudate-putamen by paired recordings in transgenic mice
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DOI：
10.1113/jphysiol.2006.114272
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发表时间：
2006-09-15
影响因子：
5.5
通讯作者：
Szabo, Bela
中科院分区：
文献类型：
--
作者：
Freiman, Ilka;Anton, Alexandra;Szabo, Bela
CB1大麻素受体在尾核-壳核的许多神经元中表达。然而，目前尚不清楚这些受体的激活如何影响不同神经元类别之间的突触传递。目的是建立一种方法来研究尾核-壳核中已识别的突触连接，并确定大麻素对这些连接的影响。采用在细小蛋白阳性快速峰值中间神经元（PV-FSNs）中表达增强绿色荧光蛋白（EGFP）的转基因小鼠制备脑切片。利用荧光特性对PV-FSNs进行了鉴定。非荧光中等神经元被认为是中等棘神经元（MSNs）。通过同时膜片钳记录已识别神经元对的突触传递。在PV-FSN -> MSN神经传递的情况下，合成大麻素受体激动剂WIN55212-2降低了传递成功率和成功突触后事件的振幅。微抑制突触后电流分析表明，WIN55212-2通过突触前抑制突触传递。WIN55212-2未引起PV-FSNs的体树突效应：膜电位、膜电流和诱发放电未发生改变。WIN55212-2也抑制了MSN ->的MSN神经传递。突触后去极化msn释放的内源性大麻素仅能微弱抑制对msn的抑制性突触输入。结果表明，结合使用转基因动物和配对记录技术，可以研究罕见神经元之间的突触连接。利用这些技术，我们发现(i) PV-FSNs和（ii） msn轴突末端的CB1受体激活导致这些轴突和它们的突触后靶点（msn）之间的gaba能突触传递的突触前抑制。大麻素优先作用于轴突终末，对神经元的体树突区域没有影响。
CB1 cannabinoid receptors are expressed in many neurons in the caudate-putamen. However, it is not known how the activation of these receptors influences synaptic transmission between different neuron classes. The aim was to establish a method for studying identified synaptic connections in the caudate-putamen, and to determine the effects of cannabinoids on these connections. Brain slices were prepared from transgenic mice expressing enhanced green fluorescent protein (EGFP) in parvalbumin-positive fast spiking interneurons (PV-FSNs). PV-FSNs were identified based on their fluorescence. Non-fluorescent medium-sized neurons were considered to be medium spiny neurons (MSNs). Synaptic transmission was studied by simultaneous patch-clamp recording from identified neuron pairs. In the case of PV-FSN -> MSN neurotransmission, the synthetic cannabinoid receptor agonist WIN55212-2 lowered the success rate of transmission and the amplitude of successful postsynaptic events. Analysis of miniature inhibitory postsynaptic currents indicated that WIN55212-2 inhibited synaptic transmission presynaptically. WIN55212-2 did not elicit somatodendritic effects in PV-FSNs: membrane potential, membrane current and evoked firing were not changed. WIN55212-2 also depressed the MSN -> MSN neurotransmission. The inhibitory synaptic input to MSNs was only weakly suppressed by endocannabinoids released by depolarized postsynaptic MSNs. The results show that the combined use of transgenic animals and paired-recording techniques allows the study of synaptic connections between rare neurons. Using these techniques, we showed that activation of CB1 receptors on axon terminals of (i) PV-FSNs and (ii) MSNs leads to presynaptic inhibition of GABAergic synaptic transmission between these axons and their postsynaptic targets, the MSNs. The cannabinoids acted preferentially on axon terminals without effects on the somatodendritic region of the neurons.