Hilz Emily N, Agee Laura A, Jun Donyun, Monfils Marie-H, Lee Hongjoo J
Department of Psychology, The University of Texas at Austin, Austin, TX, United States.
Institute for Neuroscience, The University of Texas at Austin, Austin, TX, United States.
Front Behav Neurosci. 2023 Jul 13;17:1210631. doi: 10.3389/fnbeh.2023.1210631. eCollection 2023.
Renewal is a behavioral phenomenon wherein extinction learning fails to generalize between different contextual environments, thereby representing a significant challenge to extinction-based rehabilitative therapies. Previously, we have shown that renewal of extinguished appetitive behavior differs across the estrous cycle of the female rat. In this experiment that effect is replicated and extended upon to understand how the estrous cycle may modulate contextual representation at the neuronal population level to drive renewal.
Estrous cycle stage [i.e., proestrus (P, high hormone) or metestrus/diestrus (M/D, low hormone)] was considered during two important learning and behavioral expression windows: at extinction training and during long-term memory (LTM)/renewal testing. Cellular compartment analysis of temporal activity using fluorescence hybridization (catFISH) for mRNA was conducted after the distinct context-stimulus exposures.
Rats in P during context-dependent extinction training but in a different stage of the estrous cycle during LTM and renewal testing (P-different) were shown to exhibit more renewal of conditioned foodcup (but not conditioned orienting) behavior compared to rats in other estrous cycle groups. Importantly, we discovered this depends on the order of tests. P-different rats showed differential mRNA expression in regions of the prefrontal cortex (PFC), amygdala, and hippocampus (HPC). For each case P-different rats had more co-expression (i.e., expression of both nuclear and cytoplasmic) of mRNA compared to other groups; specific to the dorsal HPC, P-different rats also had a more robust mRNA response to the extinction context exposure.
These data suggest female rats show estrous cycle state-dependent renewal of appetitive behavior, and differences in context and conditioned stimulus representation at the neuronal level may drive this effect.
恢复是一种行为现象，其中消退学习无法在不同的情境环境之间泛化，从而对基于消退的康复治疗构成重大挑战。此前，我们已经表明，雌性大鼠消退的食欲行为的恢复在发情周期中有所不同。在本实验中，我们重复并扩展了这一效应，以了解发情周期如何在神经元群体水平上调节情境表征以驱动恢复。
在两个重要的学习和行为表达窗口期间考虑发情周期阶段[即发情前期（P，高激素）或动情后期/间情期（M/D，低激素）]：在消退训练时以及在长期记忆（LTM）/恢复测试期间。在不同的情境刺激暴露后，使用荧光杂交（catFISH）对mRNA进行细胞区室时间活动分析。
与其他发情周期组的大鼠相比，在情境依赖性消退训练期间处于发情前期但在LTM和恢复测试期间处于发情周期不同阶段（P-不同）的大鼠表现出更多的条件性食杯（但不是条件性定向）行为的恢复。重要的是，我们发现这取决于测试顺序。P-不同的大鼠在前额叶皮质（PFC）、杏仁核和海马体（HPC）区域表现出不同的mRNA表达。对于每种情况，与其他组相比，P-不同的大鼠具有更多的mRNA共表达（即核和细胞质的表达）；特定于背侧HPC，P-不同的大鼠对消退情境暴露也有更强健的mRNA反应。
这些数据表明雌性大鼠表现出发情周期状态依赖性的食欲行为恢复，并且在神经元水平上情境和条件刺激表征的差异可能驱动了这种效应。
