Date of Award

4-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Biomedical Sciences

Track

Cell Biology and Physiology

Research Advisor

Jack W. Tsao, MD

Committee

Amy L. de Jongh Curry, PhD Kaushik Parthasarathi, PhD Valeria Vasquez, PhD Robert S. Waters, PhD

Keywords

Barrel subfield, Cortical reorganization, Delayed reorganization, Forelimb deafferentation, Primary somatosensory cortex, Rapid reorganization

Abstract

The goal of this study is to examine mechanisms underlying cortical reorganization in rat primary somatosensory (SI) cortex that follows forelimb deafferentation. The majority of human patients suffering from limb loss or brachial plexus avulsion injury, as well as patients that receive brachial plexus anesthesia, report phantom limb sensations/pain which are often associated with cortical reorganization. Patients with upper-limb deafferentation report sensations of the missing hand during tactile stimulation of the face, and this phenomenon has been termed hand-to-face remapping. We sought to develop a rodent model of deafferentation; our model system is the rat SI cortex barrel field present at the cortical layer IV, where neural cell clusters, called barrels, represent localized regions of the skin surface. The forepaw barrel subfield (FBS), consisting of approximately 26 barrels, receives somatotopically organized input from the contralateral glabrous and hairy skin surfaces of the forepaw. When input from the forelimb is no longer available following limb amputation, brachial plexus nerve cut or brachial plexus anesthesia, neurons in the deafferented FBS begin responding to previously unexpressed input from the lower jaw; here, we define this phenomenon as hand-to-face cortical reorganization. In this dissertation, electrophysiological mapping of SI was used to examine hand-to-face cortical reorganization in the FBS. Immediately following each type of deafferentation, lower jaw input became expressed in the rostral part of the FBS; conversely, 9-to-27 weeks after limb amputation, lower jaw input became expressed throughout the entire FBS. Anatomical tracers were used to explore the source(s) of the newly expressed lower jaw input in the deafferented rostral and caudal FBS. We identified a corticocortical projection from the neighboring lower jaw barrel subfield (LJBSF) to the rostral part of the FBS and speculate that the caudal FBS is served by a subcortical source. The present study, along with ongoing work in our lab, documents cortical reorganization in a rodent animal model, explores the source(s) of the newly expressed input, and speculates on cortical and subcortical mechanisms underlying reorganization. The goal of experiment group one was to study the lower jaw skin representation at rat somatosensory cortex (SI) as an essential first step for understanding its possible role in cortical reorganization. We performed an electrophysiology mapping of the lower jaw barrel subfield (LJBSF) in SI of Sprague-Dawley rats. In order to analyze the whole area, carbon fiber electrodes were used to record single and multiple unit responses within the layer IV of the LJBSF. Analysis of the lower jaw skin surface was performed in order to have a precise nomenclature of the skin surface to relate the structural (morphological) organization to the functional organization (physiological map) of the lower jaw in layer IV of SI. The goal of experiment group two was to report the phenomenon of hand-to-face remapping after a transient peripheral lesion (brachial plexus nerve cut, forelimb amputation) or nerve block (brachial plexus nerve anesthesia), and a permanent lesion (forelimb amputation) to study rapid remapping or delayed in time respectively. Electrophysiology mapping of the FBS was done in rapid remapping before and immediately after the forelimb deafferentation; for delayed remapping the FBS map and analysis of hand-to-face phenomenon were done after 9-to-27 weeks of the forelimb deafferentation. The goal of experiment group three was to examine the possible role of intra cortical and subcortical connections between the lower jaw and forepaw representations that likely underlies the rapid and delayed hand-to-face cortical reorganization respectively. Neural tracers, Biotinylated Dextran Amine (BDA) and Cholera Toxin B (CT-B) were used to analyze intrinsic connectivity between LJBSF and FBS areas, and also possible thalamocortical connectivity between ventral posteromedial nucleus (VPM) and LJBSF-FBS areas. In conclusion, in this study we developed a rodent animal model to study hand to face reorganization in SI using deafferentations similar to those observed in the clinic. We used anatomical tracers to examine the source(s) of the observed reorganization. Our study, may provide insight in understanding hand-to-face reorganization in humans, where we think that this may be useful for understanding cortical reorganization following major limb amputation in humans.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

https://orcid.org/0000-0001-6277-7980

DOI

10.21007/etd.cghs.2022.0588

2022-003-Morata-DOA.pdf (133 kB)
Declaration of Authorship

Available for download on Wednesday, May 17, 2023

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