Quirk Gregory J, Likhtik Ekaterina, Pelletier Joe Guillaume, Paré Denis
Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico 00732, USA.
J Neurosci. 2003 Sep 24;23(25):8800-7. doi: 10.1523/JNEUROSCI.23-25-08800.2003.
In extinction of auditory fear conditioning, rats learn that a tone no longer predicts the occurrence of a footshock. Recent lesion and unit recording studies suggest that the medial prefrontal cortex (mPFC) plays an essential role in the inhibition of conditioned fear following extinction. mPFC has robust projections to the amygdala, a structure that is known to mediate the acquisition and expression of conditioned fear. Fear conditioning potentiates the tone responses of neurons in the basolateral amygdala (BLA), which excite neurons in the central nucleus (Ce) of the amygdala. In turn, the Ce projects to the brainstem and hypothalamic areas that mediate fear responses. The present study was undertaken to test the hypothesis that the mPFC inhibits conditioned fear via feedforward inhibition of Ce output neurons. Recording extracellularly from physiologically identified brainstem-projecting Ce neurons, we tested the effect of mPFC prestimulation on Ce responsiveness to synaptic input. In support of our hypothesis, mPFC prestimulation dramatically reduced the responsiveness of Ce output neurons to inputs from the insular cortex and BLA. Thus, our findings support the idea that mPFC gates impulse transmission from the BLA to Ce, perhaps through GABAergic intercalated cells, thereby gating the expression of conditioned fear.
在听觉恐惧条件反射消退过程中,大鼠学会了一种音调不再预示足部电击的发生。最近的损伤和单位记录研究表明,内侧前额叶皮层(mPFC)在消退后对条件性恐惧的抑制中起重要作用。mPFC向杏仁核发出强大的投射,杏仁核是一个已知介导条件性恐惧习得和表达的结构。恐惧条件反射增强了基底外侧杏仁核(BLA)中神经元的音调反应,这些神经元会兴奋杏仁核中央核(Ce)中的神经元。反过来,Ce投射到介导恐惧反应的脑干和下丘脑区域。本研究旨在检验mPFC通过对Ce输出神经元的前馈抑制来抑制条件性恐惧的假设。我们从生理上确定的投射到脑干的Ce神经元进行细胞外记录,测试了mPFC预刺激对Ce对突触输入反应性的影响。为支持我们的假设,mPFC预刺激显著降低了Ce输出神经元对来自岛叶皮层和BLA输入的反应性。因此,我们的研究结果支持这样一种观点,即mPFC可能通过GABA能插入细胞控制从BLA到Ce的冲动传递,从而控制条件性恐惧的表达。