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BIDIRECTIONAL PLASTICITY SUPPORTS LEARNING AND POST-ISCHEMIC
FUNCTIONAL RECOVERY IN THE RAT STRIATUM
by
Kelly Ann Kent
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
August 2011
Copyright 2011 Kelly Ann Kent
Object Description
| Title | Bidirectional plasticity supports learning and post-ischemic functional recovery in the rat striatum |
| Author | Kent, Kelly Ann |
| Author email | kkent@usc.edu;kellyakent@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts And Sciences |
| Date defended/completed | 2011-04-29 |
| Date submitted | 2011-08-06 |
| Date approved | 2011-08-08 |
| Restricted until | 2011-08-08 |
| Date published | 2011-08-08 |
| Advisor (committee chair) | McNeill, Thomas H |
| Advisor (committee member) |
Winstein, Carolee Johnson, Deborah |
| Abstract | While stroke-related deaths have decreased in recent years, stroke is still the leading cause of long-term disability in the United States. Adequate rehabilitation is dependant upon plasticity, a multidimensional and adaptive process underlying recovery of function in both the human and rodent brain. The complexity of processes underlying plasticity in the central nervous system is still largely unknown, but manipulating this spontaneous state of the healing brain is of the utmost importance as it will allow maximum therapeutic effect. Characterization of lesion-induced local and remote rewiring, initial behavioral deficit and their long-term relationships to behavioral outcome are required to fill some of the gaps in our understanding of brain repair mechanisms after stroke. The experiments outlined in this dissertation take advantage of hypothesized neuroplasticity foundations of learning and memory, as well as an established model of forelimb motor cortex injury in rats in order to examine changes in the striatal target regions of the disrupted and intact corticofugal tracts as well as within the uninjured homotopic sensorimotor cortex. Ultimately, these studies enhance those changes and their behavioral correlates through skilled training. ❧ Our work investigates the molecular underpinnings of unilateral skilled reach task acquisition in the rat. The findings demonstrate that striatal shifts in glutamate receptor subunit phosphorylation and composition, known to support changes in synaptic strength and efficacy, accompany learning in an experience-dependent fashion. As task-specific rehabilitation is a critical component of stroke-related disability treatment, an increasing understanding of neurotransmission alterations that occur during novel motor sequence practice can play a valuable role in the pursuit of adjuvant therapies. ❧ Results presented show that naïve learning and post-ischemic re-learning share molecular support phenomena. Bi-directional (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) AMPA and (N-methyl D-aspartate) NMDA receptor changes are associated with behavioral recovery from lesion-induced impairments in an ordinal and training-dependent manner. Substantial skilled task experience, likely accompanied by morphological growth at active corticostriatal synapses, allows glutamate receptor-modulated long-term plasticity thresholds to stabilize, thereby promoting an insaturable learning environment. While loss of cortical input to the denervated striatum is likely the source of abnormal patterns of glutamate receptor expression in the hemisphere subject to lesion, disregulated inhibition within the intact cortex may initiate these changes along the corticostriatal pathway of the non-injured hemisphere. Initial behavioral deficit is an indication of both extent of lesion and underlying neurotransmitter transmission and receptor expression. ❧ Medium spiny neuron (MSN) synaptic plasticity can contribute to improved functional motor output variably in the context of different experimental paradigms. This flexibility is appropriate for the striatum's critical role in both motor learning and recovery, as it simultaneously promotes physiological adaptability and homeostasis. One of the fundamental sources of support for this elegant and malleable system may be the capacity for bi-directionality at glutamate receptors. Future studies will continue to uncover the potential for modifying these characteristics for use in innovative and effective clinical strategies. |
| Keyword | ischemia; learning; plasticity |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Kent, Kelly Ann |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-KentKellyA-255.pdf |
Description
| Title | Page 1 |
| Full text | BIDIRECTIONAL PLASTICITY SUPPORTS LEARNING AND POST-ISCHEMIC FUNCTIONAL RECOVERY IN THE RAT STRIATUM by Kelly Ann Kent A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) August 2011 Copyright 2011 Kelly Ann Kent |
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