Reichel Laboratory, Medical University of South Carolina, Department of Neuroscience, Charleston, SC, 29425, USA.
Reichel Laboratory, Medical University of South Carolina, Department of Neuroscience, Charleston, SC, 29425, USA.
Neuropharmacology. 2023 Dec 1;240:109711. doi: 10.1016/j.neuropharm.2023.109711. Epub 2023 Sep 7.
Return to methamphetamine (meth) use is part of an overarching addictive disorder hallmarked by cognitive sequela and cortical dysfunction in individuals who use meth chronically. In rats, long access meth self-administration produces object recognition memory deficits due to drug-induced plasticity within the perirhinal cortex (PRH). PRH projections are numerous and include the medial prefrontal cortex (mPFC). To evaluate the role of the PRH-mPFC reciprocal circuit in novel object recognition memory, a rgAAV encoding GFP-tagged Cre recombinase was infused into the PRH or the mPFC and rats were tested for recognition memory. On test day, one group explored both familiar and novel objects. A second group explored only familiar objects. GFP and Fos expression were visualized in the mPFC or PRH. During exploration, PRH neurons receiving input from the mPFC were equally activated by exploration of novel and familiar objects. In contrast, PRH neurons that provide input to the mPFC were disproportionately activated by novel objects. Further, the percent of Fos + cells in the PRH positively correlated with recognition memory. As such, the flow of communication appears to be from the PRH to the mPFC. In agreement with this proposed directionality, chemogenetic inhibition of the PRH-mPFC circuit impaired object recognition memory, whereas chemogenetic activation in animals with a history of long access meth self-administration reversed the meth-induced recognition memory deficit. This finding informs future work aimed at understanding the role of the PRH, mPFC, and their connectivity in meth associated memory deficits. These data suggest a more complex circuitry governing recognition memory than previously indicated with anatomical or lesion studies.
复吸是一种广泛存在的成瘾障碍的一部分，其特征是长期使用冰毒的个体存在认知后遗症和皮质功能障碍。在大鼠中，长期使用冰毒自我给药会导致物体识别记忆缺陷，这是由于药物引起的边缘下皮层（PRH）可塑性。PRH 投射众多，包括内侧前额叶皮层（mPFC）。为了评估 PRH-mPFC 相互作用回路在新物体识别记忆中的作用，rgAAV 编码 GFP 标记的 Cre 重组酶被注入 PRH 或 mPFC，然后对大鼠进行识别记忆测试。在测试日，一组大鼠同时探索熟悉和新的物体，另一组只探索熟悉的物体。在 mPFC 或 PRH 中可视化 GFP 和 Fos 表达。在探索过程中，来自 mPFC 的输入接收 PRH 神经元被新的和熟悉的物体探索同等激活。相比之下，向 mPFC 提供输入的 PRH 神经元被新物体不成比例地激活。此外，PRH 中 Fos+细胞的百分比与识别记忆呈正相关。因此，通信的流向似乎是从 PRH 到 mPFC。与这种提出的方向一致，PRH-mPFC 回路的化学遗传抑制损害了物体识别记忆，而在有长期接触冰毒自我给药史的动物中，化学遗传激活逆转了冰毒引起的识别记忆缺陷。这一发现为未来旨在理解 PRH、mPFC 及其连接在与冰毒相关的记忆缺陷中的作用的工作提供了信息。这些数据表明，与解剖学或损伤研究相比，控制识别记忆的电路更为复杂。
