Subthalamic nucleus neurons switch from single-spike activity to burst-firing mode
Subthalamic nucleus neurons switch from single-spike activity to burst-firing mode
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DOI：
10.1523/jneurosci.19-02-00599.1999
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发表时间：
1999-01-15
影响因子：
5.3
通讯作者：
Hammond, C
中科院分区：
文献类型：
--
作者：
Beurrier, C;Congar, P;Hammond, C
大鼠和灵长类帕金森病的特征之一是丘脑底核（subthalamicnucleus，STN）神经元放电模式由单一放电模式转变为混合爆发放电模式。然而，这一过程的机制尚不清楚。用细胞内和膜片钳技术观察了大鼠脑片海马神经元的内在放电模式。当膜从-41.3 +/- 1.0 mV（范围，-35至-50 mV; n = 15）超极化到-51.0 +/-1.0 mV（范围，-42至-60 mV; n = 20）时，几乎一半以单棘波模式自发放电的STN神经元具有切换到纯或混合爆发放电模式的内在特性。这种转换大大促进了代谢型谷氨酸受体与1 S，3R-ACPD的激活。突发放电模式下的复发性膜振荡是内源性的和Ca 2+依赖性的，因为在任何测试的电位下，硝苯地平（3 μ M）、Ni 2+（40 μ M）和BAPTA-AM（10-50 μ M）都能大大降低这些振荡，而TTX（1 μ M）则没有影响。相比之下，同时应用TEA（1 mM）和蜂毒肽（0.2 μ M）延长爆裂持续时间。此外，在响应于超极化电位的细胞内刺激时，在82%的测试突触神经元中记录到具有类似于自发爆发的电压和离子基础的平台电位，所有这些都显示出低阈值Ni 2+敏感的尖峰。我们建议，在爆发周期性的膜振荡的结果从顺序激活的T/R-和L-型钙电流，钙激活内向电流，和钙激活的K+电流。
The modification of the discharge pattern of subthalamic nucleus (STN) neurons from single-spike activity to mixed burst-firing mode is one of the characteristics of parkinsonism in rat and primates. However, the mechanism of this process is not yet understood. Intrinsic firing patterns of STN neurons were examined in rat brain slices with intracellular and patch-clamp techniques. Almost half of the STN neurons that spontaneously discharged in the single-spike mode had the intrinsic property of switching to pure or mixed burst-firing mode when the membrane was hyperpolarized from -41.3 +/- 1.0 mV (range, -35 to -50 mV; n = 15) to -51.0 +/- 1.0 mV(range, -42 to -60 mV; n = 20). This switch was greatly facilitated by activation of metabotropic glutamate receptors with 1S,3R-ACPD. Recurrent membrane oscillations underlying burst-firing mode were endogenous and Ca2+-dependent because they were largely reduced by nifedipine (3 mu M), Ni2+ (40 mu M), and BAPTA-AM (10-50 mu M) at any potential tested, whereas TTX(1 mu M) had no effect. In contrast, simultaneous application of TEA (1 mM) and apamin (0.2 mu M) prolonged burst duration. Moreover, in response to intracellular stimulation at hyperpolarized potentials, a plateau potential with a voltage and ionic basis similar to those of spontaneous bursts was recorded in 82% of the tested STN neurons, all of which displayed a low-threshold Ni2+- sensitive spike. We propose that recurrent membrane oscillations during bursts result from the sequential activation of T/R- and L-type Ca2+ currents, a Ca2+-activated inward current, and Ca2+-activated K+ currents.