División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México México City, Federal District, México.
Front Syst Neurosci. 2011 Mar 29;5:15. doi: 10.3389/fnsys.2011.00015. eCollection 2011.
Suprathreshold corticostriatal responses recorded from medium spiny neurons (MSNs) from the direct and indirect pathways of the basal ganglia are different. Their differences readily distinguish D(1)- and D(2)-type receptor expressing MSNs in both bacterial artificial chromosome-transgenic mice and their control littermates as well as in rats: indirect pathway neurons are more excitable than direct pathway neurons revealing autoregenerative spikes underlying their spike trains, whereas direct pathway neurons exhibit more prolonged plateau potentials and spike trains. SFK 81297, a selective agonist for D(1)-class receptors enhanced corticostriatal responses in direct pathway neurons, while quinelorane, a selective agonist for D(2)-class receptors reduced orthodromic and autoregenerative responses in indirect pathway neurons thus making both neuron classes similarly excitable. Because dopaminergic postsynaptic actions target Ca(V)1 (L) class voltage-gated calcium channels in MSNs, we hypothesized that these channels are involved and can explain a part of the dopaminergic actions on corticostriatal integration. Both 2.5 μM nicardipine and 400 nM calciseptine, selective Ca(V)1 channel blockers, reduced corticostriatal responses in both D(1)- and D(2)-receptor expressing neurons, respectively. A previous blockade of Ca(V)1 channels occluded the actions of dopamine agonists in both neuronal classes. In contrast, a Ca(V)1 (L) channel activator, 2.5 μM Bay K 8644, enhanced corticostriatal responses in neurons from both pathways. It is concluded that Ca(V)1 intrinsic currents mediate a part of the dopaminergic modulation during orthodromic synaptic integration of cortical inputs in both classes of MSNs.
基底神经节直接和间接通路中的中脑皮层神经元（MSNs）记录到的阈上皮层纹状体反应不同。这些差异可以很容易地区分细菌人工染色体转基因小鼠及其对照同窝仔鼠以及大鼠中的 D1 型和 D2 型受体表达的 MSNs：间接通路神经元比直接通路神经元更易兴奋，表现出自发性再生尖峰，而直接通路神经元则表现出更长的平台电位和尖峰序列。D1 类受体的选择性激动剂 SFK 81297 增强了直接通路神经元的皮层纹状体反应，而 D2 类受体的选择性激动剂喹那洛尔则减少了间接通路神经元的传入和自发放电反应，从而使这两种神经元类型具有相似的兴奋性。由于多巴胺能突触后作用靶向 MSNs 中的 Ca(V)1（L）类电压门控钙通道，我们假设这些通道参与其中，并可以解释多巴胺对皮层纹状体整合的部分作用。2.5μM 尼卡地平和 400nM calciseptine，分别是 Ca(V)1 通道的选择性阻断剂，均可减少 D1 和 D2 受体表达神经元的皮层纹状体反应。先前阻断 Ca(V)1 通道可使两种神经元类型的多巴胺激动剂作用闭塞。相比之下，Ca(V)1（L）通道激活剂 2.5μM Bay K 8644 增强了来自两条通路的神经元的皮层纹状体反应。结论是，Ca(V)1 内在电流介导了多巴胺在两类 MSNs 的皮层输入的顺行突触整合过程中的部分调制作用。
