Collaborative Research: Cortical Perineuronal Net Regulation of Maternal Caregiving Behaviors

积极的社交互动通常包括个人之间非常有益的接触。个人如何感知社交接触取决于许多因素，包括他们的生殖状态。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，这对高度敏感的母亲照顾和后代发育至关重要。关于母亲的大脑在怀孕期间和产后早期如何变化来促进婴儿触摸的积极感知，科学知识非常少。这个项目将研究随着怀孕的进展和母亲获得早期护理经验，大脑皮层中接受触摸相关信息的特定区域如何对婴儿的触摸暗示变得更加敏感。该项目还将通过新的学生教育课程、为学生提供新的研究体验、公共动物园和博物馆展品，以及通过指导来自代表性不足群体的下一代脑科学家，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个领域，并增加生物和行为科学的多样性。本项目中的实验将研究母亲对后代触摸的积极感受性的神经基础，重点是皮质周围神经网(PNNS)的作用。女性生殖和成为母亲的开始涉及到广泛的神经可塑性，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参与处理触摸的皮质部位，包括初级躯体感觉皮质(S1；介导触觉辨别)和岛叶皮质(IC；处理触摸的情感成分)。皮质的可塑性受周围神经元网(PNNS)、胞外基质结构和小白蛋白+GABA能中间神经元近端树突的调节。PNN是突触可塑性的物理和分子障碍，在感觉和行为显著变化的时期，这些可塑性的“主要调节器”的表达变化。最近的实验报告了与PNN在大鼠S1面部微触觉区域过度表达有关的母体行为受损。目前的项目测试了压倒一切的假设，即女性生殖涉及S1和IC中PNN表达的变化，并且这些变化改变了对母亲照顾的触觉调节至关重要的皮质功能。这一假设将在雌性大鼠身上进行验证：(1)使用组织化学和RT-qPCR来确定PNN及其相关的mRNAs在整个自然雌性生殖过程中的变化，以响应模仿怀孕的外源类固醇激素，以及对反复幼鼠暴露的响应，以及(2)使用病毒和化学策略来确定PNN在S1或IC中表达不足或过表达对母亲照料行为的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.