Other - Novel Experimental/Analytic Approaches/Tools

The Answer is the Cellular Function: Electrophysiology of iPS-cell Derived and Porcine Sensory Neurons

Human sensory neurons isolated from the dorsal root ganglion (DRGs) are not easily assessed and rodent DRGs display substantial differences compared to humans. Thus, we use pig DRGs, as their skin and innervation of it is more similar to humans, especially for displaying sleeping nociceptors much more frequently compared to rodent models. When performing patch clamp recordings, we use an electrical stimulation paradigm which was shown to activate sleeping nociceptors in microneurography recordings in order to classify the dissociated neurons by their function. This in-depth characterization will be compared to the electrophysiology of neurons derived of induced pluripotent stem cells (iPS-cells) of probands and patients carrying a disease-causing mutation.

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Framing the Question: What are Sleeping Human Nociceptors? Why do Classes of C-fibers Show a Specific Response Pattern to Electrical Stimulation?

In this talk the core questions, wich shall be handled by the other speakers during this session will be framed: What are sleeping human nociceptors? Why do classes of C-fibers show a specific response pattern to electrical stimulation? Functional nociceptor classification as obtained by microneurogrpahic recordings will be described in health and disease. Special focus will be placed upon properties and possible functional roles of the so called sleeping or silent nociceptors, which are the opposite of “silent” in chonic pain.

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The Answer is All in the Genes: RNASeq of Human Sensory Neurons

Ted Price’s presentation will focus on molecular phenotyping of human sensory neurons using single cell and spatial RNA sequencing. The focus of the talk will be on human and porcine silent nociceptors and what we know about their molecular makeup. The presentation will include data slides, but also opportunities to dive deeper into the data using on-demand data visualization tools that the lab has developed. These can be found at sensoryomics.com.

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The Answer is the Synthesis of Both: PatchSeq Takes our Knowledge in Neuron Classification to the Next Level

In this talk, Dr. Tripathy will give an overview of methods for integrating gene expression with electrophysiology and morphology based cellular atlases. He will give an overview of the powerful Patch-seq method, which allows researchers to combine information across multiple modalities. He will discuss how this approach can be used in a number of contexts, including in the context of identifying cell types responsible for neuropathic pain.

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What Are Sleeping C-Fiber Nociceptors? Taking a Question from Human Physiology to Experiment

Studies in humans often reveal questions about patho-physiological phenomena which are not easily addressed by basic science. Lab research on the other hand often provides answers that are hard to translate into clinics.
In this new workshop format, we will address the following questions arising from studies on human subjects: What are sleeping human nociceptors? Why do classes of C-fibers show a specific response pattern to electrical stimulation? Sleeping nociceptors are linked to neuropathic pain, but cannot ordinarily be activated by any physiological stimulus, and electrical activation using sine waves is not fiber type specific.
Thus, their basic (non-sensitized) state in humans is not characterized and the electrical basis for responsiveness to sine waves is unclear. Therefore, targeting these fibers to prevent or treat neuropathic pain remains an unresolved issue.
We will frame the question and hear the answers of basic scientists: The electrical responsiveness of pig sensory neurons to sine waves will be compared to the excitability of iPS-cell-derived sensory neurons. Using RNAseq on human sensory neurons, specific subclasses based on transcriptomics are identified. Combining both approaches using PatchSeq will create a synthesis and can take neuronal classification to a level that has not previously been achieved.

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