Date of Award

2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Wenqin Luo

Abstract

Commonly, different regions of sensory maps are used to meet separate functional requirements. For the somatosensory system (which mediates sensation from the skin including touch, pain, and related modalities), the distal limbs have special behavioral importance for exploration and object manipulation. Accordingly, the hands and fingertips show heightened sensitivity for both touch and pain sensation in human subjects. In contrast to the touch system, the neural mechanisms for region-specific pain sensation are poorly understood. Despite over a century of research into the neural basis of pain, past work has not clearly defined the functional organization of the pain system across the body (somatotopic) map. In Chapter 2, we use a novel genetic mouse line to map the organization of one major class of mammalian pain-sensory neurons (the Mrgprd+ non-peptidergic nociceptors) across the body map. While we find no obvious peripheral mechanisms for high sensitivity in the distal limbs (mouse plantar paw skin has a low density of Mrgprd+ terminals, and single-cell arbor areas are comparable between paw and trunk skin), we reveal a novel region-specific organization in the spinal cord terminal arbors of these neurons. Specifically, paw and trunk neurons grow ‘round’ and ‘long’ arbor morphologies, respectively, such that paw neurons have a wider mediolateral spread in the spinal cord. We show that this region-specific morphology closely correlates with increased signal transmission for paw pain circuits. We conclude that region-specific organization of Mrgprd+ spinal cord terminals provides a possible mechanism for the high pain sensitivity of the distal limbs. In Chapter 3, we investigate potential developmental mechanisms for region-specific arbor morphologies. Disruption of peripheral target innervation does not alter their central arbor morphologies, suggesting that this central somatotopic difference develops independent of cues/processes from the periphery. However, this difference is present from very early developmental stages, suggesting that pre-programming mechanisms might govern this somatotopic pattern. Collectively, this work reveals that region-specific organization is a fundamental principle for the pain system with clear implications for our understanding of pain in both normal and pathological conditions.

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