Wai Valerie, Roberts Lauren, Michaud Jana, Bent Leah R, Clark Andrea L
Department of Human Health and Nutritional Sciences, College of Biological Science, University of Guelph, Guelph, ON, Canada.
Front Neuroanat. 2021 Mar 2;15:628711. doi: 10.3389/fnana.2021.628711. eCollection 2021.
Afferent neurons and their mechanoreceptors provide critical sensory feedback for gait. The anatomical distribution and density of afferents and mechanoreceptors influence sensory feedback, as does mechanoreceptor function. Electrophysiological studies of hind paw skin reveal the different types of afferent responses and their receptive fields, however, the anatomical distribution of mechanoreceptor endings is unknown. Also, the role of integrin α1β1 in mechanoreceptor function is unclear, though it is expressed by keratinocytes in the stratum basale where it is likely involved in a variety of mechanotransduction pathways and ion channel functionalities. For example, it has been shown that integrin α1β1 is necessary for the function of TRPV4 that is highly expressed by afferent units. The purpose of this study, therefore, was to determine and compare the distribution of mechanoreceptors across the hind paw skin and the footfall patterns of -null and wild type mice. The -null mouse is lacking the integrin α1 subunit, which binds exclusively to the β1 subunit, thus rendering integrin α1β1 nonfunctional while leaving the numerous other pairings of the β1 subunit undisturbed. Intact hind paws were processed, serially sectioned, and stained to visualize mechanoreceptors. Footfall patterns were analyzed as a first step in correlating mechanoreceptor distribution and functionality. Merkel cells and Meissner-like corpuscles were present, however, Ruffini endings and Pacinian corpuscles were not observed. Meissner-like corpuscles were located exclusively in the glabrous skin of the footpads and digit tips, however, Merkel cells were found throughout hairy and glabrous skin. The increased density of Merkel cells and Meissner-like corpuscles in footpads 1 and 3 and Meissner-like corpuscles in footpad 4 suggests their role in anteroposterior balance, while Meissner-like corpuscle concentrations in digits 2 and 5 support their role in mediolateral balance. Finally, a larger density of Meissner-like corpuscles in footpads 3 and 4 in male -null mice compared to wild type controls paves the way for future site-specific single fiber recordings to provide insight into the role of integrin α1β1 in tactile mechanotransduction.
传入神经元及其机械感受器为步态提供关键的感觉反馈。传入神经元和机械感受器的解剖分布及密度会影响感觉反馈,机械感受器的功能也会产生同样的影响。对后爪皮肤的电生理研究揭示了不同类型的传入反应及其感受野,然而,机械感受器末梢的解剖分布尚不清楚。此外,整合素α1β1在机械感受器功能中的作用尚不清楚,尽管它由基底层的角质形成细胞表达,可能参与多种机械转导途径和离子通道功能。例如,已经表明整合素α1β1是传入单位高度表达的TRPV4功能所必需的。因此,本研究的目的是确定并比较后爪皮肤中机械感受器的分布以及整合素α1β1基因敲除小鼠和野生型小鼠的脚步落点模式。整合素α1β1基因敲除小鼠缺乏仅与β1亚基结合的整合素α1亚基,从而使整合素α1β1失去功能,同时β1亚基的许多其他配对不受影响。对完整的后爪进行处理,连续切片并染色以观察机械感受器。作为关联机械感受器分布和功能的第一步,对脚步落点模式进行了分析。存在默克尔细胞和类梅斯纳小体,然而,未观察到鲁菲尼终末和环层小体。类梅斯纳小体仅位于脚垫和指尖的无毛皮肤中,然而,默克尔细胞在有毛和无毛皮肤中均有发现。脚垫1和3中默克尔细胞和类梅斯纳小体密度的增加以及脚垫4中类梅斯纳小体密度的增加表明它们在前-后平衡中的作用,而第2和5趾中类梅斯纳小体的集中支持它们在内外侧平衡中的作用。最后,与野生型对照相比,雄性整合素α1β1基因敲除小鼠脚垫3和4中类梅斯纳小体的密度更大,这为未来进行位点特异性单纤维记录以深入了解整合素α1β1在触觉机械转导中的作用铺平了道路。