Section on In Vivo Neural Function, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health Bethesda, MD, USA.
Front Integr Neurosci. 2009 Oct 30;3:28. doi: 10.3389/neuro.07.028.2009. eCollection 2009.
Previous studies showed that dopamine depletion leads to both changes in firing rate and in neuronal synchrony in the basal ganglia. Since dopamine D1 and D2 receptors are preferentially expressed in striatonigral and striatopallidal medium spiny neurons, respectively, we investigated the relative contribution of lack of D1 and/or D2-type receptor activation to the changes in striatal firing rate and synchrony observed after dopamine depletion. Similar to what was observed after dopamine depletion, co-administration of D1 and D2 antagonists to mice chronically implanted with multielectrode arrays in the striatum caused significant changes in firing rate, power of the local field potential (LFP) oscillations, and synchrony measured by the entrainment of neurons to striatal local field potentials. However, although blockade of either D1 or D2 type receptors produced similarly severe akinesia, the effects on neural activity differed. Blockade of D2 receptors affected the firing rate of medium spiny neurons and the power of the LFP oscillations substantially, but it did not affect synchrony to the same extent. In contrast, D1 blockade affected synchrony dramatically, but had less substantial effects on firing rate and LFP power. Furthermore, there was no consistent relation between neurons changing firing rate and changing LFP entrainment after dopamine blockade. Our results suggest that the changes in rate and entrainment to the LFP observed in medium spiny neurons after dopamine depletion are somewhat dissociable, and that lack of D1- or D2-type receptor activation can exert independent yet interactive pathological effects during the progression of Parkinson's disease.
先前的研究表明，多巴胺耗竭会导致基底神经节中神经元的放电率和同步性发生变化。由于多巴胺 D1 和 D2 受体分别优先表达在纹状体苍白球和纹状体黑质神经元中，因此我们研究了缺乏 D1 和/或 D2 型受体激活对多巴胺耗竭后观察到的纹状体放电率和同步性变化的相对贡献。与多巴胺耗竭后观察到的情况类似，在慢性植入多电极阵列的小鼠中，同时给予 D1 和 D2 拮抗剂会导致放电率、局部场电位 (LFP) 振荡的功率以及通过神经元对纹状局部场电位的同步性发生显著变化。然而，尽管阻断 D1 或 D2 型受体均会导致类似严重的运动不能，但对神经活动的影响却不同。阻断 D2 受体显著影响中脑神经元的放电率和 LFP 振荡的功率，但对同步性的影响程度不同。相比之下，D1 阻断显著影响同步性，但对放电率和 LFP 功率的影响较小。此外，多巴胺阻断后，改变神经元放电率和改变 LFP 同步性之间没有一致的关系。我们的研究结果表明，在多巴胺耗竭后中脑神经元中观察到的 LFP 放电率和同步性的变化有些可分离，并且缺乏 D1 或 D2 型受体激活在帕金森病进展过程中可能产生独立但相互作用的病理效应。
