Laboratorio de Memoria y Cognición Molecular, Instituto de Neurociencia Cognitiva y Traslacional, Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)-Fundación INECO-Universidad Favaloro, 1071 Ciudad Autónoma de Buenos Aires, Argentina.
Grupo de Neurociencia de Sistemas, Instituto de Fisiología y Biofísica "Houssay" (IFIBIO "Houssay"), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1121ABG Ciudad Autónoma de Buenos Aires, Argentina.
J Neurosci. 2022 Aug 24;42(34):6620-6636. doi: 10.1523/JNEUROSCI.0740-21.2022. Epub 2022 Jul 19.
Active forgetting occurs in many species, but how behavioral control mechanisms influence which memories are forgotten remains unknown. We previously found that when rats need to retrieve a memory to guide exploration, it reduces later retention of other competing memories encoded in that environment. As with humans, this retrieval-induced forgetting relies on prefrontal control processes. Dopaminergic input to the prefrontal cortex is important for executive functions and cognitive flexibility. We found that, in a similar way, retrieval-induced forgetting of competing memories in male rats requires prefrontal dopamine signaling through D receptors. Blockade of medial prefrontal cortex D receptors as animals encountered a familiar object impaired active forgetting of competing object memories as measured on a later long-term memory test. Inactivation of the ventral tegmental area produced the same pattern of behavior, a pattern that could be reversed by concomitant activation of prefrontal D receptors. We observed a bidirectional modulation of retrieval-induced forgetting by agonists and antagonists of D receptors in the medial prefrontal cortex. These findings establish the essential role of prefrontal dopamine in the active forgetting of competing memories, contributing to the shaping of retention in response to the behavioral goals of an organism. Forgetting is a ubiquitous phenomenon that is actively promoted in many species. The very act of remembering some experiences can cause forgetting of others, in both humans and rats. This retrieval-induced forgetting process is thought to be driven by inhibitory control signals from the prefrontal cortex that target areas where the memories are stored. Here we started disentangling the neurochemical signals in the prefrontal cortex that are essential to retrieval-induced forgetting. We found that, in rats, the release of dopamine in this area, acting through D receptors, was essential to causing active forgetting of competing memories. Inhibition of D receptors impaired forgetting, while activation increased forgetting. These findings are important, because the mechanisms of active forgetting and their linkage to goal-directed behavior are only beginning to be understood.
主动遗忘发生在许多物种中，但行为控制机制如何影响哪些记忆被遗忘尚不清楚。我们之前发现，当老鼠需要检索记忆来指导探索时，它会减少以后对该环境中其他竞争记忆的保留。与人类一样，这种检索诱导的遗忘依赖于前额叶控制过程。多巴胺能输入到前额叶皮层对于执行功能和认知灵活性很重要。我们发现，以类似的方式，雄性大鼠中竞争记忆的检索诱导遗忘需要通过 D 受体的前额叶多巴胺信号。在动物遇到熟悉物体时，阻断内侧前额叶皮层 D 受体，会损害随后的长期记忆测试中对竞争物体记忆的主动遗忘。腹侧被盖区的失活产生了相同的行为模式，通过同时激活前额叶 D 受体可以逆转这种模式。我们观察到内侧前额叶皮层 D 受体激动剂和拮抗剂对检索诱导遗忘的双向调节。这些发现确立了前额叶多巴胺在竞争记忆主动遗忘中的重要作用，有助于根据生物体的行为目标来塑造保留。遗忘是一种普遍存在的现象，在许多物种中都被积极促进。在人类和大鼠中，记住某些经历的行为本身就会导致对其他经历的遗忘。这种检索诱导的遗忘过程被认为是由前额叶皮层的抑制性控制信号驱动的，这些信号针对的是存储记忆的区域。在这里，我们开始梳理前额叶皮层中对检索诱导遗忘至关重要的神经化学信号。我们发现，在大鼠中，该区域多巴胺的释放，通过 D 受体起作用，对于引起竞争记忆的主动遗忘是必不可少的。D 受体的抑制会损害遗忘，而激活会增加遗忘。这些发现很重要，因为主动遗忘的机制及其与目标导向行为的联系才刚刚开始被理解。
