Findings have shown that anterior insular cortex (aIC) lesions disrupt the maintenance of drug addiction, while imaging studies suggest that connections between amygdala and aIC participate in drug-seeking. However, the role of the BLA → aIC pathway in rewarding contextual memory has not been assessed. Using a cre-recombinase under the tyrosine hydroxylase (TH+) promoter mouse model to induce a real-time conditioned place preference (rtCPP), we show that photoactivation of TH+ neurons induced electrophysiological responses in VTA neurons, dopamine release and neuronal modulation in the aIC. Conversely, memory retrieval induced a strong release of glutamate, dopamine, and norepinephrine in the aIC. Only intra-aIC blockade of the glutamatergic N-methyl-D-aspartate receptor accelerated rtCPP extinction. Finally, photoinhibition of glutamatergic BLA → aIC pathway produced disinhibition of local circuits in the aIC, accelerating rtCPP extinction and impairing reinstatement. Thus, activity of the glutamatergic projection from the BLA to the aIC is critical for maintenance of rewarding contextual memory.

研究结果表明，前岛叶皮质（aIC）病变破坏了药物成瘾的维持，而影像学研究表明杏仁核和aIC之间的联系参与了药物寻找。但是，尚未评估BLA→aIC途径在奖励情境记忆中的作用。在酪氨酸羟化酶（TH +）启动子小鼠模型下使用cre重组酶诱导实时条件性位置偏爱（rtCPP），我们显示TH +神经元的光活化在aIC中诱导了VTA神经元的电生理反应，多巴胺释放和神经元调节。相反，记忆恢复在aIC中引起谷氨酸，多巴胺和去甲肾上腺素的强烈释放。只有aIC内对谷氨酸能N-甲基-D-天冬氨酸受体的阻断会加速rtCPP的灭绝。最后，谷氨酸能BLA→aIC途径的光抑制作用会导致aIC局部回路的抑制，加速rtCPP的灭绝并损害恢复。因此，从BLA到aIC的谷氨酸能投射的活性对于维持有益的背景记忆至关重要。