Department of Anatomy and Cell Biology, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
J Neurosci. 2011 Apr 6;31(14):5300-12. doi: 10.1523/JNEUROSCI.4718-10.2011.
The cannabinoid CB1 receptor system is critically involved in the control of associative fear memory formation within the amygdala-prefrontal cortical pathway. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the prelimbic division (PLC) of the medial prefrontal cortex (mPFC). However, the precise role of CB1 receptor transmission within the BLA during the processing of fear memory is not fully understood. We examined the potential role of BLA CB1 receptor transmission during an olfactory fear-conditioning procedure in rats by pharmacologically modulating CB1 cannabinoid transmission directly within the BLA. We report that blockade of BLA CB1 receptor transmission prevents the acquisition of associative fear memory, while having no effect on the recall or consolidation of these memories. In contrast, intra-BLA activation of CB1 receptor transmission or blockade of endocannabinoid reuptake strongly potentiated the emotional salience of normally subthreshold fear-conditioning stimuli. In addition, pharmacological inactivation of the mPFC before intra-BLA CB1 activation blocked CB1-receptor-mediated potentiation of fear memory formation. In vivo single-unit electrophysiological recordings within the PLC revealed that modulation of BLA CB1 receptor transmission strongly influences neuronal activity within subpopulations of PLC neurons, with blockade of intra-BLA CB1 receptor transmission inhibiting spontaneous PLC neuronal activity and activation of CB1 receptors producing robust activation, in terms of neuronal firing frequency and bursting activity. Thus, cannabinoid transmission within the BLA strongly modulates the processing of associative fear memory via functional interactions with PLC neuronal populations.
大麻素 CB1 受体系统在杏仁核-前额皮质通路中控制联想性恐惧记忆形成中起着至关重要的作用。CB1 受体在大脑结构中高度集中，这些结构对于情绪处理至关重要，包括基底外侧杏仁核（BLA）和内侧前额皮质（mPFC）的前扣带回皮质（PLC）。然而，BLA 内 CB1 受体传递在恐惧记忆处理中的精确作用尚不完全清楚。我们通过在 BLA 内直接调节 CB1 大麻素传递，研究了 BLA 内 CB1 受体传递在大鼠嗅觉恐惧条件反射程序中的潜在作用。我们报告说，阻断 BLA 内 CB1 受体传递可阻止联想性恐惧记忆的获得，而对这些记忆的回忆或巩固没有影响。相比之下，BLA 内 CB1 受体传递的激活或内源性大麻素再摄取的阻断强烈增强了正常阈下恐惧条件反射刺激的情绪显著性。此外，在 BLA 内 CB1 激活之前对 mPFC 进行药理学失活，阻断了 CB1 受体介导的恐惧记忆形成的增强。PLC 内的体内单细胞电生理记录表明，BLA CB1 受体传递的调制强烈影响 PLC 神经元亚群内的神经元活动，BLA 内 CB1 受体传递的阻断抑制 PLC 神经元的自发活动，而 CB1 受体的激活则产生强大的激活，表现为神经元放电频率和爆发活动。因此，BLA 内的大麻素传递通过与 PLC 神经元群体的功能相互作用，强烈调节联想性恐惧记忆的处理。
