Rutgers University, United States.
Rutgers University, United States.
Neurobiol Learn Mem. 2019 May;161:175-191. doi: 10.1016/j.nlm.2019.04.004. Epub 2019 Apr 13.
Arc (Activity-regulated cytoskeleton-associated protein) is an effector neuronal immediate-early gene (IEG) and has been closely linked to behaviorally-induced neuronal plasticity. The present studies examined the regionally-selective, dissociable patterns of Arc expression induced by Pavlovian trace fear conditioning, delay fear conditioning, and contextual fear conditioning as well as novel context exposure. This research was guided by anatomical studies identifying heterogeneity of connectivity across the transverse (CA1, CA3) and septo-temporal (dorsal vs. ventral) axes of the hippocampus; companion neuropsychological experiments suggest that these subregions likely play functionally dissociable roles in different forms of hippocampal-dependent learning. Hence the primary goal of the present study was to characterize the expression of Arc protein across both the septotemporal and transverse axes of the hippocampus induced by hippocampal dependent trace fear conditioning and compare these expression patterns to those induced by other fear conditioning paradigms. A second goal of these studies was to explore which specific paradigmatic features of the fear conditioning task itself are responsible for the observed patterns of Arc expression. The results of these studies suggest that, within the dorsal hippocampus, Arc expression in CA3 induced by trace fear conditioning may play a unique role in representing the context, while Arc protein expression within ventral CA3 may reflect CS processing. Arc protein expression in dorsal and ventral CA1 are likely not meaningfully involved in trace fear conditioning as there is either a lack of significant enhancement (dorsal CA1) or enhancement is not unique to subjects trained in trace fear conditioning (ventral CA1). The specific regional pattern of Arc protein enhancement induced by trace fear conditioning may reflect the unique temporal parameters of the task which critically engages the hippocampus in processing both contextual representations as well as the explicit CS. This additional hippocampal processing may account for the greater enhancement in Arc protein in dorsal and ventral CA3 for subjects trained in trace fear conditioning compared to novel context exposure, or contextual and delay fear conditioning.
Arc（活性调节细胞骨架相关蛋白）是一种效应神经元即时早期基因（IEG），与行为诱导的神经元可塑性密切相关。本研究检测了由条件性恐惧痕迹条件反射、延迟条件反射和情景条件反射以及新情景暴露诱导的 Arc 表达的区域选择性、可分离模式。本研究的指导思想是基于解剖学研究，该研究确定了海马体的横切（CA1、CA3）和隔颞（背侧与腹侧）轴之间连接的异质性；伴随的神经心理学实验表明，这些亚区可能在不同形式的海马体依赖性学习中发挥功能可分离的作用。因此，本研究的主要目标是描述由海马体依赖性痕迹恐惧条件反射诱导的 Arc 蛋白在海马体的隔颞和横切轴上的表达，并将这些表达模式与其他恐惧条件反射范式进行比较。这些研究的第二个目标是探索恐惧条件反射任务本身的哪些特定范式特征是导致观察到的 Arc 表达模式的原因。这些研究的结果表明，在背侧海马体中，由痕迹恐惧条件反射诱导的 CA3 中的 Arc 表达可能在表示情景方面发挥独特作用，而 CA3 内的 Arc 蛋白表达可能反映 CS 处理。背侧和腹侧 CA1 中的 Arc 蛋白表达可能与痕迹恐惧条件反射无关，因为缺乏明显的增强（背侧 CA1）或增强不是仅在进行痕迹恐惧条件反射训练的动物中（腹侧 CA1）。由痕迹恐惧条件反射诱导的 Arc 蛋白增强的特定区域模式可能反映了任务的独特时间参数，该参数使海马体在处理上下文表示以及明确的 CS 方面受到严格的影响。这种额外的海马体处理可能解释了在进行痕迹恐惧条件反射训练的动物中，Arc 蛋白在背侧和腹侧 CA3 中的增强比新情景暴露或情景和延迟恐惧条件反射更大。
