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雄性和雌性大鼠不同条件性恐惧反应的行为和神经关联

Behavioral and neural correlates of diverse conditioned fear responses in male and female rats.

作者信息

Mitchell Julia R, Vincelette Lindsay, Tuberman Samantha, Sheppard Vivika, Bergeron Emmett, Calitri Roberto, Clark Rose, Cody Caitlyn, Kannan Akshara, Keith Jack, Parakoyi Abigail, Pikus MaryClare, Vance Victoria, Ziane Leena, Brenhouse Heather, Laine Mikaela A, Shansky Rebecca M

机构信息

Northeastern University, Boston, MA.

Smith College, Northampton, MA.

出版信息

bioRxiv. 2024 Aug 21:2024.08.20.608817. doi: 10.1101/2024.08.20.608817.

Abstract

Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock ("shock response"). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.

摘要

巴甫洛夫式恐惧条件反射是一种广泛应用的工具,用于模拟啮齿动物的联想学习。几十年来,该领域主要使用雄性啮齿动物,并专注于一种单一的条件性恐惧反应:僵住。然而,我们实验室和其他机构最近的研究发现,窜动是一种雌性偏向的条件性反应,其特征是在恐惧条件反射箱中出现类似逃跑的动作。它还伴随着一种行为表型:与非窜动者和雄性相比,窜动者的僵住行为可靠地减少,并且在受到足部电击(“电击反应”)时达到更高的速度。然而,电击反应与条件性窜动之间的关系尚不清楚。本研究调查了这种联系是否是由于窜动者、非窜动者和雄性在厌恶刺激的一般处理上存在差异。在包括皮质酮测量、听觉惊吓测试和对热痛的敏感性等多种模式下,发现窜动者对厌恶刺激并不更具反应性或敏感性,而且在某些情况下,它们对非窜动者和雄性的反应性似乎更低。对恐惧条件反射后参与疼痛和恐惧处理的区域中的cFos活性分析,确定了暴露于低强度和高强度足部电击的窜动者、非窜动者和雄性之间不同的表达模式。这些研究结果进一步加深了我们对窜动者、非窜动者和雄性之间差异的理解,并强调了研究恐惧条件反射中的个体差异作为恐惧状态指标的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdee/11370446/a25dc1e94d15/nihpp-2024.08.20.608817v1-f0001.jpg

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