Neural Mechanisms Underlying IC/BPS

摘要 间质性膀胱炎/膀胱痛综合征(IC/BPS)是一种虚弱的情况，失去对膀胱的控制和 严重的膀胱疼痛对膀胱充盈有影响。IC/BPS的潜在机制还知之甚少。令人信服的研究 表明通过直接投射到脊髓的脑干可以直接调节伤害性信息的处理 膀胱功能。在我们的初步研究中，我们已经确定了脑干神经元的不同群体 投射到脊髓。在这里，我们将确定这些不同的脑干神经元在 IC/BPS的病理学。我们将确定IC/BPS是否会导致这些不同群体的适应不良变化。 我们将使用光遗传学、解剖示踪、活体钙成像、切片电生理学和核糖核酸 测序以确定IC/BPS是否导致这些电路中细胞和系统级别的功能变化。 这些变化是否会驱动IC/BPS？逆转这些不适应变化能缓解IC/BPS吗？总而言之，这 这项工作将揭示这种神经回路在IC/BPS中的具体作用。这种丰富的信息可以有广泛的 在IC/BPS治疗中设计更安全的治疗药物的潜在新方向的含义。

Abstract Interstitial cystitis/bladder pain syndromes (IC/BPS) is a debilitating condition with loss of bladder control and severe bladder pain on bladder filling. Mechanisms underlying IC/BPS are poorly understood. Compelling studies show that the brainstem via direct projection to the spinal cord can directly modulate nociceptive processing and bladder function. In our preliminary studies, we have identified distinct populations of the brainstem neurons that project to the spinal cord. Here we will determine the precise roles of these distinct brainstem neurons in the pathology of IC/BPS. We will determine if IC/BPS leads to maladaptive changes in these distinct populations. We will use optogenetics, anatomical tracing, in vivo calcium imaging, slice electrophysiology and RNA sequencing to determine if IC/BPS leads to functional changes at the cellular and systems level in these circuits. Do these changes drive IC/BPS? Does reversing these maladaptive changes relieve IC/BPS? Together, this work will reveal the specific roles for this neural circuits in IC/BPS. This rich information can have broad implications for potential new direction in designing safer therapeutic drugs in treatment of the IC/BPS.