Bayer Hugo, Hassell James E, Oleksiak Cecily R, Garcia Gabriela M, Vaughan Hollis L, Juliano Vitor A L, Maren Stephen
Department of Psychological and Brain Sciences, Texas A&M University, College Station.
Department of Pharmacology, São Paulo University, São Paulo.
bioRxiv. 2024 Mar 27:2024.03.23.586410. doi: 10.1101/2024.03.23.586410.
The infralimbic (IL) division of the medial prefrontal cortex (mPFC) is a crucial site for extinction of conditioned fear memories in rodents. Recent work suggests that neuronal plasticity in the IL that occurs during (or soon after) fear conditioning enables subsequent IL-dependent extinction learning. We therefore hypothesized that pharmacological activation of the IL after fear conditioning would promote the extinction of conditioned fear. To test this hypothesis, we characterized the effects of post-conditioning infusions of the GABA receptor antagonist, picrotoxin, into the IL on extinction of auditory conditioned freezing in male and female rats. In four experiments, we found that picrotoxin injections performed immediately, 24 hours, or 13 days after fear conditioning reduced conditioned freezing to the auditory conditioned stimulus (CS) during both extinction training and extinction retrieval; this effect was observed up to two weeks after picrotoxin infusions. Interestingly, inhibiting protein synthesis inhibition in the IL immediately after fear conditioning prevented the inhibition of freezing by picrotoxin injected 24 hours later. Our data suggest that the IL encodes an inhibitory memory during the consolidation of fear conditioning that is necessary for future fear suppression.
内侧前额叶皮质(mPFC)的边缘下(IL)分区是啮齿动物条件性恐惧记忆消退的关键部位。最近的研究表明,在恐惧条件反射期间(或之后不久)IL中发生的神经元可塑性能够使随后依赖IL的消退学习成为可能。因此,我们推测在恐惧条件反射后对IL进行药理学激活会促进条件性恐惧的消退。为了验证这一假设,我们研究了在雄性和雌性大鼠的IL中注射GABA受体拮抗剂印防己毒素对条件性听觉僵住行为消退的影响,注射是在恐惧条件反射之后进行的。在四项实验中,我们发现,在恐惧条件反射后立即、24小时或13天进行印防己毒素注射,在消退训练和消退检索期间均会减少对听觉条件刺激(CS)的条件性僵住行为;在注射印防己毒素后长达两周都能观察到这种效应。有趣的是,在恐惧条件反射后立即抑制IL中的蛋白质合成,可阻止24小时后注射的印防己毒素对僵住行为的抑制。我们的数据表明,IL在恐惧条件反射巩固过程中编码一种抑制性记忆,这对未来的恐惧抑制是必要的。