Queen's University, Centre for Neuroscience Studies, Kingston, Ontario K7L 3N6, Canada.
J Neurosci. 2010 Aug 25;30(34):11493-500. doi: 10.1523/JNEUROSCI.1550-10.2010.
Impulse control suppresses actions that are inappropriate in one context, but may be beneficial in others. The medial prefrontal cortex (mPFC) mediates this process by providing a top-down signal to inhibit competing responses, although the mechanism by which the mPFC acquires this ability is unknown. To that end, we examined synaptic changes in the mPFC associated with learning to inhibit an incorrect response. Rats were trained in a simple response inhibition task to withhold responding until a signal was presented. We then measured synaptic plasticity of excitatory synapses in the mPFC, using whole-cell patch-clamp recordings, in brain slices prepared from trained rats. Response inhibition training significantly increased the relative contribution of AMPA receptors to the overall EPSC in prelimbic, but not infralimbic, neurons of the mPFC. This potentiation of synaptic transmission closely paralleled the acquisition and extinction of response inhibition. Using a retrograde fluorescent tracer, we observed that these plastic changes were selective for efferents projecting to the ventral striatum, but not the dorsal striatum or amygdala. Therefore, we suggest that response inhibition is encoded by a selective strengthening of a subset of corticostriatal projections, uncovering a synaptic mechanism of impulse control. This information could be exploited in therapeutic interventions for disorders of impulse control, such as addiction, attention deficit-hyperactivity disorder, and schizophrenia.
冲动控制抑制了在一种情境下不适当的行为，但在其他情境下可能是有益的。内侧前额叶皮层（mPFC）通过提供自上而下的信号来抑制竞争反应来介导这个过程，尽管 mPFC 获得这种能力的机制尚不清楚。为此，我们研究了与学习抑制错误反应相关的 mPFC 中的突触变化。大鼠在简单的反应抑制任务中接受训练，直到出现信号才做出反应。然后，我们使用全细胞膜片钳记录，在从受过训练的大鼠中制备的脑片中测量 mPFC 中兴奋性突触的突触可塑性。反应抑制训练显著增加了外侧前额叶皮层（mPFC）中 AMPA 受体对整体 EPSC 的相对贡献，但在 infralimbic 神经元中没有。这种突触传递的增强与反应抑制的获得和消退密切平行。使用逆行荧光示踪剂，我们观察到这些塑性变化是针对投射到腹侧纹状体的传出纤维的选择性变化，而不是投射到背侧纹状体或杏仁核的传出纤维。因此，我们认为反应抑制是由皮质纹状体投射的一个子集的选择性增强来编码的，揭示了冲动控制的一种突触机制。这一信息可以在冲动控制障碍的治疗干预中得到利用，如成瘾、注意力缺陷多动障碍和精神分裂症。
