Collaborative Research: Cortical Perineuronal Net Regulation of Maternal Caregiving Behaviors

合作研究：母亲护理行为的皮质神经周围网络调节

• 批准号: 2336907
• 负责人: KEERTHI KRISHNAN
• 金额: $ 61万
• 依托单位: University of Tennessee Knoxville
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2336907&HistoricalAwards=false
• 关键词: Collaborative; Research; Cortical; Perineuronal; Net

Positive social interactions often include highly rewarding touch among individuals. How individuals perceive social touch depends on many factors, including their reproductive state. One important example of this influence of reproductive state is that postpartum mothers find touch cues from infants extremely positive, which is essential for highly sensitive maternal caregiving and offspring development. There is very little scientific knowledge about how the maternal brain changes across pregnancy and early postpartum to promote the positive perception of infant touch. This project will study how specific areas of the cerebral cortex that receive touch-related information become more sensitive to infant touch cues as pregnancy progresses and as mothers gain early caregiving experience. This project will also broaden educational opportunities and scientific outreach through new student education courses, new research experiences for students, public zoo and museum exhibits, and by mentoring the next generation of brain scientists from underrepresented groups. The scientific approach and techniques used in these studies will be taught to students from a range of ethnic, social, and economic backgrounds, with the goal of attracting them to this field and increasing diversity in the biological and behavioral sciences. The experiments in this project will investigate the neural basis of maternal positive receptivity to offspring touch, with a focus on the role of cortical perineuronal nets (PNNs). Female reproduction and the onset of motherhood involve widespread neuroplasticity that underlies this critical social interaction. Importantly, this neuroplasticity occurs in cortical sites involved in processing touch, including the primary somatosensory cortex (S1; mediates tactile discrimination) and the insular cortex (IC; processes affective components of touch). Cortical plasticity is regulated by perineuronal nets (PNNs), extracellular matrix structures surrounding the somata and proximal dendrites of parvalbumin+ GABAergic interneurons. PNNs are physical and molecular barriers to synaptic plasticity and expression of these “master regulators” of plasticity changes across times of significant sensory and behavioral flux. Recent experiments reported impaired maternal behavior associated with PNN overexpression in the rat S1 facial microvibrissae area. The current project tests the overarching hypothesis that female reproduction involves changes in PNN expression in S1 and IC, and that these changes alter cortical function critical for tactile regulation of maternal caregiving. This hypothesis will be tested in female rats by: (1) using histochemistry and rt-qPCR to determine changes in PNNs and associated mRNAs in S1 and IC across natural female reproduction, in response to exogenous steroid hormones mimicking pregnancy, and in response to repeated pup exposure and (2) using viral and chemical strategies to determine the effects of PNN underexpression or overexpression in the S1 or IC on maternal caregiving behaviors.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

积极的社交互动通常包括个体之间高度有益的触摸。个体如何看待社交触摸取决于许多因素，其中包括生殖状态的这种影响的一个重要例子是产后母亲发现婴儿的触摸暗示非常积极，这是至关重要的。对于高度敏感的母亲护理和后代发育，关于母亲大脑在怀孕和产后早期如何变化以促进婴儿触摸的积极感知的科学知识很少。相关信息对婴儿触摸提示变得更加敏感随着怀孕的进展和母亲获得早期护理经验，该项目还将通过新的学生教育课程、学生的新研究经验、公共动物园和博物馆展览以及指导来自代表性不足的下一代脑科学家来扩大教育机会和科学推广。这些研究中使用的科学方法和技术将教授给来自不同种族、社会和经济背景的学生，目的是吸引他们进入这一领域并增加生物和行为科学实验的多样性。该项目将研究的神经基础母亲对后代触摸的积极接受，重点关注皮质神经元网络（PNN）的作用，女性生殖和母性的开始涉及广泛的神经可塑性，这是这种关键的社会互动的基础，重要的是，这种神经可塑性发生在涉及处理触摸的皮质部位。皮质可塑性受神经周围调节神经网络（PNN）、小清蛋白+ GABA能中间神经元的胞体和近端树突周围的细胞外基质结构是突触可塑性的物理和分子障碍，并且这些“主调节因子”的表达在明显的感觉和行为流动受损时发生变化。与大鼠 S1 面部微触须区域 PNN 过度表达相关的母性行为当前的项目测试了雌性生殖涉及 PNN 表达变化的总体假设。 S1 和 IC 中的变化，并且这些变化改变了对于母体护理的触觉调节至关重要的皮质功能，该假设将通过以下方式在雌性大鼠中进行测试：（1）使用组织化学和 rt-qPCR 来确定 S1 和 IC 中 PNN 和相关 mRNA 的变化。 IC 跨越自然雌性生殖，响应模拟妊娠的外源类固醇激素，响应幼仔的反复暴露，以及 (2) 使用病毒和化学策略来确定 S1 或 S1 中 PNN 表达不足或过度表达的影响IC 关于孕产妇护理行为。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。