Darting across space and time: parametric modulators of sex-biased conditioned fear responses.

Darting across space and time: parametric modulators of sex-biased conditioned fear responses.
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跨越空间和时间:性别偏见条件恐惧反应的参数调制器。

DOI:
10.1101/lm.053587.122
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发表时间:
2022-07
期刊:
影响因子:
2
通讯作者:
Shansky, Rebecca M.
Shansky, Rebecca M.
中科院分区:
医学4区
文献类型:
--
作者:
Mitchell, Julia R.;Trettel, Sean G.;Li, Anna J.;Wasielewski, Sierra;Huckleberry, Kylie A.;Fanikos, Michaela;Golden, Emily;Laine, Mikaela A.;Shansky, Rebecca M.

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巴甫洛夫恐惧条件反射是研究啮齿动物联想学习的一种广泛使用的行为范式。尽管早期认识到受试者可能参与各种条件反应和非条件反应,但在过去的几十年里,该领域已经缩小了研究范围,将测量冻结作为条件恐惧的唯一指标。我们之前报道过雌性大鼠比雄性大鼠更有可能进行飞奔,这是一种类似逃跑的条件反射,与更高的休克反应性有关。为了确定实验参数如何影响男性和女性的投掷频率,我们操纵了诸如腔室大小、冲击强度和试验次数等因素。为了更好地捕捉动物的恐惧相关行为,我们开发了ScaredyRat,这是一个开源的定制Python工具,用于分析Noldus ethovision生成的原始数据文件,以识别目标并量化条件和非条件反应。我们发现,就像冻结一样,条件反射性的飞镖事件随着实验的改变而扩大。虽然大多数飞镖发生在雌性身上,但我们发现,随着训练的延长,飞镖也会出现在雄性身上。总的来说,我们的数据表明,飞镖反映了条件反应中的行为转换,这是个体动物性别、休克反应和实验参数的产物,强调了在经典学习范式中,需要仔细考虑性别作为生物变量。
Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage in a variety of both conditioned and unconditioned responses, the last several decades have seen the field narrow its focus to measure freezing as the sole indicator of conditioned fear. We previously reported that female rats were more likely than males to engage in darting, an escape-like conditioned response that is associated with heightened shock reactivity. To determine how experimental parameters contribute to the frequency of darting in both males and females, we manipulated factors such as chamber size, shock intensity, and number of trials. To better capture fear-related behavioral repertoires in our animals, we developed ScaredyRat, an open-source custom Python tool that analyzes Noldus Ethovision-generated raw data files to identify darters and quantify both conditioned and unconditioned responses. We found that, like freezing, conditioned darting occurrences scale with experimental alterations. While most darting occurs in females, we found that with an extended training protocol, darting can emerge in males as well. Collectively, our data suggest that darting reflects a behavioral switch in conditioned responding that is a product of an individual animal's sex, shock reactivity, and experimental parameters, underscoring the need for careful consideration of sex as a biological variable in classic learning paradigms.
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