Neural coding of cutaneous temperature in the spinal cord and its modulation under persistent pain condition
Abstract/Contents
- Abstract
- Temperature has a profound influence on all biochemical processes in an organism. In most animals, the nervous system enables them to detect environmental temperature. In this case, animals actively control over their metabolism by adjusting their body temperature. In the past two decades, scientists have discovered various molecular detectors of cutaneous temperature in the primary sensory neurons. Temperature above (or below) their activation thresholds triggers ion influx through these channels, thus converting temperature information into nerve impulses. Despite a growing body of literature on the molecular and cellular mechanisms of temperature detection in the peripheral nervous system, little is known about how temperature is encoded in the central nervous system. The initial stage of integration of somatosensory information occurs the spinal cord. Here, I developed an in vivo calcium imaging system to investigate the coding of cutaneous temperature in the spinal cord. In contrast to the primary sensory neurons in the DRG that encode temperature in a modality-specific manner, the spinal cord uses a population intensity code to encode temperature intensity. Once spinal neurons reach their thresholds, responses to heat faithfully reflect the absolute temperature whereas responses to cold selectively signal the change of temperature. Heat-responsive spinal neurons receive major inputs from TRPV1+ DRG neurons, while cold-responsive neurons receive TRPM8+ DRG inputs as well as novel TRPV1+ DRG inputs that are selectively activated by strong cold. The thermosensory system is adaptable to change. Upon tissue injury, the thermosensory system adjust its sensitivity so that animals can better attend to the injured area. This plasticity is hijacked under chronic pain condition, making it a debilitating disease in human. To understand the change of the neural coding of cutaneous temperature, I examined the representations of temperature in the spinal cord by combining in vivo calcium imaging and various persistent pain models. I show that formalin- or prostaglandin E2-induced inflammation dramatically increases spinal responses to heating and decreases responses to cooling. The reduction of cold response is largely eliminated upon ablation of TRPV1-expressing primary sensory neurons, indicating a crossover inhibition of cold response from heat inputs in the spinal cord. Interestingly, the increase in sensitivity to heat and decrease in sensitivity to cold largely occur in a group of dually tuned neurons that respond to both cold and heat, providing a neural substrate that mediate the altered sensitivity in inflammatory pain. By contrast, oxaliplatin, a chemotherapy medication, increases spinal responses to cooling and suppresses responses to heating. Together, our results provide the first comprehensive examination of the neural coding of heat and cold in the spinal cord and its plasticity under pathological conditions.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Ran, Chen |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Chen, Xiaoke |
| Primary advisor | Luo, Liqun, 1966- |
| Thesis advisor | Chen, Xiaoke |
| Thesis advisor | Luo, Liqun, 1966- |
| Thesis advisor | Barres, Ben |
| Thesis advisor | Malenka, Robert C |
| Advisor | Barres, Ben |
| Advisor | Malenka, Robert C |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Chen Ran. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Chen Ran
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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