Date of Award

Spring 1-1-2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology & Neuroscience

First Advisor

Daniel Barth

Second Advisor

Linda Watkins

Third Advisor

Jerry Rudy

Abstract

The insular cortex is the often forgotten 5th lobe of the brain, and examination of its functional anatomy as well as its role in behavior is still in its infancy. To elucidate these unknown details a complete mapping of the functional anatomy of the caudal granular insular cortex (CGIC), as well as its relative position to other somatosensory maps was undertaken revealing its mislabeling as the parietal ventral region (PV). Using this unprecedented localization of CGIC, targeted lesions revealed its role in the maintenance of long-term allodynia in the chronic constriction injury (CCI) model of neuropathic pain. In addition the efferent outputs were examined using neuroanatomical tract tracing techniques. Using this knowledge as an anatomical blueprint, a possible spinal-cortico-spinal loop was uncovered using laminar multi-unit analysis of the lumbar dorsal horn combined with evoked stimulation and inhibition of sciatic, CGIC, and primary somatosensory cortex (SI). Further, an electrophysiological signature of disinhibition was seen in CGIC two weeks post CCI, which was verified with laminar multi-unit analysis and protein analysis. Acute disinhibition of CGIC mimicked cold allodynia behavior in an operant two-plate temperature discrimination task. These data suggest that disinhibition of CGIC plays a critical role in the maintenance of allodynia following CCI in the rat.

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