Onn Shao-Pii, Wang Xiao-Bin
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Eur J Neurosci. 2005 Jun;21(11):2975-92. doi: 10.1111/j.1460-9568.2005.04122.x.
A distinct increase in cell firing activity is reported in prefrontal cortex during working memory tasks. The afferents that modulate this activity are not yet identified. Using in vivo intracellular recording and labelling of prefrontal cortical pyramidal neurons in anaesthetized rats, we systematically evaluated the influences of afferent projections arising from the ventral tegmental area (VTA) and mediodorsal thalamus (MD) by phasic electrical stimulation with a range of stimulus frequencies. Both VTA- and MD-responsive pyramidal neurons exhibited extensive intracortical axon arborization. Neither single shocks to the VTA at 0.2 Hz, nor low frequency trains of stimuli at 1-4 Hz (< 5 Hz) interrupted the periodicity of membrane bistability in bistable pyramidal neurons. However, high-frequency VTA-train stimulation (10-50 Hz) interrupted the bistability, and produced sustained membrane depolarizations accompanied by intense tonic firing in a frequency-dependent manner. Electrical stimulation of MD (10-50 Hz) did not produce sustained activity in the same PFC neurons. Thus, the sustained activity induced by high-frequency VTA trains is input selective. This effect of VTA-train stimulation was attenuated by systemic injection of the D1 receptor antagonist, SCH 23390, and blocked by acute dopamine (DA) depletion produced via alpha-methyl-para-tyrosine pre-treatment, suggesting that sustained cortical activity is mediated by DA. Chemical stimulation of VTA via intra-VTA infusion of NMDA induced sustained activity similar to VTA-train stimulation. Thus, while both VTA- and MD-responsive pyramidal neurons exhibited extensive intracortical axon arborization, VTA synapses (as opposed to MD synapses) may be critically positioned in the dendritic arborizations of anterior cingulate cortical pyramidal neurons, which may allow their modulation of sustained activity in prefrontal bistable neurons.
据报道，在工作记忆任务期间前额叶皮质的细胞放电活动有明显增加。调节这种活动的传入神经尚未确定。我们使用体内细胞内记录和标记麻醉大鼠前额叶皮质锥体神经元的方法，通过一系列刺激频率的相位电刺激，系统地评估了腹侧被盖区（VTA）和背内侧丘脑（MD）传入投射的影响。对VTA和MD有反应的锥体神经元均表现出广泛的皮质内轴突分支。无论是0.2 Hz的VTA单次电击，还是1-4 Hz（<5 Hz）的低频刺激序列，都不会中断双稳态锥体神经元膜双稳态的周期性。然而，高频VTA序列刺激（10-50 Hz）会中断双稳态，并以频率依赖的方式产生持续的膜去极化，伴有强烈的紧张性放电。MD的电刺激（10-50 Hz）在相同的前额叶皮质神经元中不会产生持续活动。因此，高频VTA序列诱导的持续活动具有输入选择性。VTA序列刺激的这种效应被全身性注射D1受体拮抗剂SCH 23390减弱，并被通过α-甲基-对-酪氨酸预处理产生的急性多巴胺（DA）耗竭所阻断，这表明持续的皮质活动是由DA介导的。通过VTA内注入NMDA对VTA进行化学刺激可诱导出与VTA序列刺激相似的持续活动。因此，虽然对VTA和MD有反应的锥体神经元均表现出广泛的皮质内轴突分支，但VTA突触（与MD突触相对）可能在前扣带回皮质锥体神经元的树突分支中处于关键位置，这可能使其能够调节前额叶双稳态神经元的持续活动。
