División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510, México City, Mexico.
Global Institutes on Addiction, 1221 Brickell Ave, Miami, FL33131, USA.
Commun Biol. 2020 Mar 20;3(1):139. doi: 10.1038/s42003-020-0862-z.
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，前岛叶皮层（aIC）损伤会破坏药物成瘾的维持，而影像学研究表明杏仁核和 aIC 之间的连接参与了觅药行为。然而，杏仁核外侧核（BLA）→aIC 通路在奖赏性情境记忆中的作用尚未得到评估。使用酪氨酸羟化酶（TH+）启动子下的 cre 重组酶诱导实时条件性位置偏好（rtCPP），我们发现，TH+神经元的光激活诱导 VTA 神经元产生电生理反应、aIC 中的多巴胺释放和神经元调节。相反，记忆检索会在 aIC 中引起强烈的谷氨酸、多巴胺和去甲肾上腺素释放。只有 aIC 内的谷氨酸能 N-甲基-D-天冬氨酸受体阻断剂才能加速 rtCPP 的消退。最后，光抑制谷氨酸能 BLA→aIC 通路会导致 aIC 局部回路的去抑制，加速 rtCPP 的消退，并损害复燃。因此，来自 BLA 的谷氨酸能投射到 aIC 的活动对于维持奖赏性情境记忆至关重要。
