Chang J Y, Janak P H, Woodward D J
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Neuroscience. 2000;99(3):433-43. doi: 10.1016/s0306-4522(00)00218-9.
Up to 31 neurons per animal were simultaneously recorded from the medial prefrontal cortex and nucleus accumbens in 15 rats during i.v. cocaine self-administration sessions, using a multi-channel, single-unit recording technique. Alterations of neuronal activity (both excitatory and inhibitory) were found a few seconds before each lever press for cocaine infusion; we have called these pre-lever press neuronal activations "anticipatory responses". A detailed video analysis revealed that these neuronal firing alterations were associated with specific portions of the behavioral sequence performed before each lever press in both recording areas. Some of the simultaneously recorded neurons displayed similar firing patterns in relation to a given behavioral episode within the behavioral sequence (turning, raising head, etc.), while others fired at different times relative to each behavioral event. Cross-correlational analyses revealed inter-regional and intra-regional correlated firing patterns between pairs of simultaneously recorded medial prefrontal cortex and nucleus accumbens neurons. This correlated firing occurred in the neurons with and without anticipatory responses, although the incidence of correlations between anticipatory neuron pairs was much higher than that between non-anticipatory neuron pairs (18.4% vs 3.6%). Many correlated neuron pairs displayed a time lag in the peak of correlational activity that indicated a temporal sequence in correlated activity. In contradiction to our hypothesis, the temporal pattern of correlation reveals that there are more cases in which nucleus accumbens neurons fired ahead of medial prefrontal cortex neurons. The results suggest that multiple mesocorticolimbic neuronal circuits may code sequential steps during the behavioral sequence performed to obtain an infusion of cocaine. The observed correlated firing between the medial prefrontal cortex and the nucleus accumbens indicates that dynamic, coherent activity occurs within the mesocorticolimbic circuit. Because this circuit is hypothesized to drive drug-seeking behavior, we suggest that this correlated firing between the nucleus accumbens and the medial prefrontal cortex may participate in the control of cocaine self-administration. In addition, the finding that correlated activity within the nucleus accumbens more often precedes that of the medial prefrontal cortex suggests that the nucleus accumbens may play a prime role in the initiation of cocaine self-administration.
在静脉注射可卡因自我给药实验期间，采用多通道单单元记录技术，对15只大鼠的内侧前额叶皮质和伏隔核同时进行记录，每只动物最多记录31个神经元。在每次按压杠杆以注入可卡因前几秒，发现神经元活动（包括兴奋性和抑制性）发生改变；我们将这些按压杠杆前的神经元激活称为“预期反应”。详细的视频分析显示，这些神经元放电改变与两个记录区域中每次按压杠杆前执行的行为序列的特定部分相关。一些同时记录的神经元在行为序列中的特定行为片段（转身、抬头等）表现出相似的放电模式，而其他神经元则相对于每个行为事件在不同时间放电。交叉相关分析揭示了同时记录的内侧前额叶皮质和伏隔核神经元对之间的区域间和区域内相关放电模式。这种相关放电在有和没有预期反应的神经元中均有发生，尽管预期神经元对之间的相关性发生率远高于非预期神经元对之间的相关性发生率（18.4%对3.6%）。许多相关神经元对在相关活动峰值处显示出时间滞后，表明相关活动存在时间序列。与我们的假设相反，相关性的时间模式显示，伏隔核神经元比内侧前额叶皮质神经元更早放电的情况更多。结果表明，多个中脑皮质边缘神经元回路可能在执行获取可卡因注射的行为序列过程中编码连续步骤。内侧前额叶皮质和伏隔核之间观察到的相关放电表明中脑皮质边缘回路内发生了动态、连贯的活动。由于该回路被认为驱动觅药行为，我们认为伏隔核和内侧前额叶皮质之间的这种相关放电可能参与可卡因自我给药的控制。此外，伏隔核内的相关活动比内侧前额叶皮质的相关活动更常提前出现这一发现表明，伏隔核可能在可卡因自我给药的启动中起主要作用。
