The chronobiology of somatosensation

我们的研究小组研究调节感觉神经元模式（即对机械，热和伤害性刺激的反应）的神经免疫相互作用。由这些神经元的不同亚群表达的离子通道介导许多这些效应，并且最近发现通过免疫因子（包括细胞因子/趋化因子、金属蛋白酶和生长因子）的存在直接和间接地改变。在这个新的发现补助金提交，我们将建立在我的实验室最近的发现，研究如何时间生物学节律可以调节神经免疫通信和改变体感行为在体内和体外感觉神经元的活动。* * 我们研究计划的首要目标是确定调节神经元激活/致敏的新机制和细胞内信号通路。虽然我们通常使用损伤模型来探索这些相互作用，但越来越明显的是，由于识别出的候选对象数量庞大，很难确定感兴趣的特定目标。我实验室最近的一项发现表明，在小鼠的黑暗阶段，对辐射热刺激的热敏感性是不存在的。这一新颖而令人兴奋的发现表明，时间生物学节律可以用于健康，未受伤的动物，以确定可能调节这些行为效应的配体-受体相互作用，而不必依赖损伤/疾病模型。其他研究小组已经表明，在初始状态下，离子通道/受体和免疫介质受到昼夜节律的调节。因此，我们推测，特定的神经免疫细胞内的信息传递途径和受体配体对调节的时间生物学的节奏，改变离子通道的活动和体感功能。本提案的具体目标是：* 1。通过关注外部（光）和内部（分子钟）线索来表征躯体感觉的昼夜节律控制[PhD1，MSc1，BSc1，2];* 2。确定有助于躯体感觉的时间生物学控制的细胞类型[PhD1，Msc2，BSc3];和 * 3.识别通过时间生物学节律改变的分子线索以改变离子通道活性/功能[PhD1，MSc 3，Bsc 4，5]。**生物节律控制着几乎所有动物的各种生理过程;感觉神经元表达的离子通道/受体与分泌的免疫介质之间的相互作用改变了物种间的行为活动。因此，这项研究可以通过推进我们对这三个看似不同的系统之间相互作用的理解来影响神经科学，免疫学和时间生物学领域。这里概述的研究计划也将通过培训研究生和本科生HQP收集，分析和传播使用各种现代生物和生物化学技术收集的数据，使加拿大和加拿大人受益。

Our research group investigates neuro-immune interactions that modulate sensory neuron modalities (i.e. responses to mechanical, thermal and nociceptive stimuli). Ion channels expressed by distinct subsets of these neurons mediate many of these effects, and have recently been found to be directly and indirectly altered by the presence of immune factors including cytokines/chemokines, metalloproteases, and growth factors. In this new Discovery Grant submission, we will build on recent discoveries in my laboratory to investigate how chronobiological rhythms can regulate neuro-immune communication and alter somatosensory behaviour in vivo and sensory neuron activity in vitro. ******The over-arching goal of our research program is to identify novel mechanisms and intracellular signalling pathways that regulate neuronal activation/sensitization. While we commonly used injury models to explore these interactions, it has become increasingly clear that it is difficult to pinpoint specific targets of interest, due to the large number of candidates identified. A recent finding in my laboratory shows that thermal sensitivity to a radiant heat stimulus is absent during the dark phase in mice. This novel and exciting finding suggests that chronobiological rhythms can be used in healthy, uninjured animals to identify ligand-receptor interactions that may modulate these behavioural effects instead of having to rely injury/disease models. Other groups have shown that ion channels/receptors and immune mediators are modulated by circadian rhythms in the naïve state. Therefore, we hypothesize that specific neuro-immune intracellular messaging pathways and receptor-ligand pairs are regulated by chronobiological rhythms to alter ion channel activity and somatosensory function. The specific Aims of this proposal are to:***1. Characterize the circadian control of somatosensation, by focusing on external (light) and internal (molecular clock) cues [PhD1, MSc1, BSc1,2];***2. Determine the cell type(s) contributing to chronobiological control of somatosensation [PhD1, Msc2, BSc3]; and***3. Identifying the molecular cues altered by chronobiological rhythms to alter ion channel activity/function [PhD1, MSc3, Bsc4,5].******Biological rhythms control various physiological processes in almost all animals; interactions between ion channels/receptors expressed by sensory neurons and secreted immune mediators alter behavioural activity across species. Thus, this study can impact the fields of neuroscience, immunology, and chronobiology by advancing our understanding of the interactions that occur between the three seemingly disparate systems. The research plan outlined here will also benefit Canada and Canadians by training graduate and undergraduate HQP in the collection, analysis and dissemination of data gathered using a diverse set of modern biological and biochemical techniques.