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Williams, Erika

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Williams

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Erika

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Williams, Erika
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    Neural Mechanisms of Mechanosensation Within the Body
    (2018-05-15) Williams, Erika
    The ability to detect mechanical forces plays a critical role in organism behavior and physiology. One of the fundamental means by which we interact with our environment is through touch, which includes the ability to sense mechanical events such as pressure, impact, vibration, and changes in joint position. Similarly, one of the fundamental cues used by internal organ systems to regulate behavior and physiological responses is mechanical force within the body. Sensory systems in the intestinal tract detect stretch as these organs fill with and move food, playing a powerful role in the modulation of eating behavior. In addition, sensory systems also monitor the expansion and relaxation of the lungs during breathing to regulate respiration. Similarly, accurate monitoring of pressure within the vascular system plays a key role in regulation of cardiovascular function. Eating, breathing, and blood circulation constitute basic needs, yet our understanding of the sensory neurobiology in control of these functions is limited. To date, the molecular mechanosensors required remain unknown. However, the discovery of the mammalian mechanosensor Piezo2 raises the interesting possibility that this molecule is not only involved in detection of external mechanical cues in our skin, but may also sub-serve detection of mechanical cues within the internal organs of the body.
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    Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity
    (eLife Sciences Publications, Ltd, 2014) Chiu, Isaac; Barrett, Lee; Williams, Erika; Strochlic, David E.; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Greg; Roberson, David; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen; Woolf, Clifford
    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001
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    Coding of Internal Senses: Vagal Gut-to-Brain Circuits
    (2016-05-17) Williams, Erika; Andermann, Mark; Corey, David; Saper, Clifford; Horn, Charles
    Our ability to detect features of environments in and around us is fundamental. Organisms have developed highly specialized systems to allow for transduction of a broad variety of stimuli to convey sensory information to the nervous system. In addition to traditionally appreciated external sensory systems, such as sight, smell, taste and touch, organisms also posses internal sensory systems to detect changes in physiological state. One key body-to-brain connection is via cranial nerve X, the vagus nerve. The vagus nerve innervates most major organ systems, transmits information from peripheral organs to the brainstem, and plays a critical role in the regulation of diverse physiological processes. However, the organization of this sensory system, and direct links between response properties, terminal morphology, and signaling mechanisms is not currently available for many vagal neuron types. To study the peripheral representation of autonomic inputs, we developed a vagal ganglion imaging preparation for large-scale parallel analysis of single neuron responses in vivo. Using this preparation, we can record responses evoked by a broad array of peripherally applied stimuli, including stretch in the lung, stomach, and intestine, responses to inhaled carbon dioxide, and to chemical cues perfused through the intestinal lumen. This work allows for a careful description of response properties of vagal sensory neurons, and their organization within the ganglion. Furthermore, to link response properties of vagal sensory neuron subsets to specific anatomical phenotypes and physiological roles, we developed a genetic strategy to molecularly define neuron subsets in the context of in vivo imaging. We identified one neuron subset marked by the gut hormone receptor Glp1r that responds to mechanical distension in the gastrointestinal tract, forms stereotyped mechano-sensitive terminals, and whose activation increases gastric pressure. A second neuron subset, marked by Gpr65, detects chemical cues in the intestine, projects into intestinal villi, and causes cessations of gastric contractions. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology.