A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response.

IF 3.8 3区 医学 Q2 NEUROSCIENCES Frontiers in Molecular Neuroscience Pub Date : 2025-01-22 eCollection Date: 2025-01-01 DOI:10.3389/fnmol.2025.1347539
Allie Lipshutz, Victoria Saltz, Kristin R Anderson, Alessia Manganaro, Dani Dumitriu
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Abstract

Introduction: The neurobiological basis for individual variability in behavioral responses to stimuli remains poorly understood. Probing the neural substrates that underlie individual variability in stress responses may open the door for preventive approaches that use biological markers to identify at-risk populations. New developments of viral neuronal tracing tools have led to a recent increase in studies on long range circuits and their functional role in stress responses and social behavior. While these studies are necessary to untangle largescale connectivity, most social behaviors are mediated and fine-tuned by local subregional circuitry.

Methods: In order to probe this local, interregional connectivity, we present a new combination of a neuronal tracing system with immediate early gene immunohistochemistry for examining structural and functional connectivity within the same animal. Specifically, we combine a retrograde transsynaptic rabies tracing system with cFos colocalization immediately after an acute stressor to elucidate local structural and stress-activated connectivity within the amygdala complex in female and male mice.

Results and discussion: We show how specific structural and functional connections can predict individual variability along a spectrum of social approach/avoidance following acute social defeat stress. We demonstrate how our robust method can be used to elucidate structural and functional differences in local connectivity that mediate individual variability in behavioral response.

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一种局部追踪技术探索行为反应中个体变异的杏仁核内功能和结构相关性。
对刺激的行为反应的个体差异的神经生物学基础仍然知之甚少。探索应激反应中个体差异背后的神经基质,可能为利用生物标志物识别高危人群的预防方法打开大门。病毒神经元追踪工具的新发展导致最近对远程电路及其在应激反应和社会行为中的功能作用的研究增加。虽然这些研究对于解开大规模连接是必要的,但大多数社会行为都是由局部分区域电路介导和微调的。方法:为了探索这种局部,区域间的连通性,我们提出了一种新的神经元追踪系统与即时早期基因免疫组化的结合,用于检查同一动物体内的结构和功能连通性。具体来说,我们将逆行狂犬病跨突触追踪系统与急性应激源后立即的cfo共定位相结合,以阐明雌性和雄性小鼠杏仁核复合体内局部结构和应激激活的连接。结果和讨论:我们展示了特定的结构和功能连接如何预测急性社会失败应激后社会接近/回避的个体变异性。我们展示了我们的稳健方法如何用于阐明调节行为反应个体差异的局部连接的结构和功能差异。
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来源期刊
CiteScore
5.70
自引率
2.10%
发文量
669
审稿时长
14 weeks
期刊介绍: Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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