Molecular Mechanisms Responsible for Functional Cortical Plasticity
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Washington University in St. Louis Washington University Open Scholarship Arts & Sciences Electronic Theses and Dissertations Arts & Sciences Spring 5-15-2019 Molecular Mechanisms Responsible for Functional Cortical Plasticity During Development and after Focal Ischemic Brain Injury Andrew Wiggen Kraft Washington University in St. Louis Follow this and additional works at: https://openscholarship.wustl.edu/art_sci_etds Part of the Neuroscience and Neurobiology Commons Recommended Citation Kraft, Andrew Wiggen, "Molecular Mechanisms Responsible for Functional Cortical Plasticity During Development and after Focal Ischemic Brain Injury" (2019). Arts & Sciences Electronic Theses and Dissertations. 1825. https://openscholarship.wustl.edu/art_sci_etds/1825 This Dissertation is brought to you for free and open access by the Arts & Sciences at Washington University Open Scholarship. It has been accepted for inclusion in Arts & Sciences Electronic Theses and Dissertations by an authorized administrator of Washington University Open Scholarship. For more information, please contact [email protected]. WASHINGTON UNIVERSITY IN ST. LOUIS Division of Biology and Biomedical Sciences Neurosciences Dissertation Examination Committee: Jin-Moo Lee, Chair Joseph Culver Nico Dosenbach Marcus Raichle Bradley Schlaggar Abraham Snyder Molecular Mechanisms Responsible for Functional Cortical Plasticity During Development and after Focal Ischemic Brain Injury by Andrew Wiggen Kraft A dissertation presented to The Graduate School of Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy May 2019 St. Louis, Missouri © 2019, Andrew Kraft Table of Contents List of Figures ............................................................................................................... iii Acknowledgements ......................................................................................................ix Abstract ......................................................................................................................... x Chapter 1: Introduction and Perspective .................................................................... 1 1.1 Recovery after ischemic stroke ........................................................................ 2 1.2 Current approaches to stroke rehabilitative therapy ......................................... 2 1.3 Animal models of recovery after ischemic injury .............................................. 3 1.4 Systems-level plasticity in recovery after focal ischemic injury ......................... 4 1.5 Overview of functional brain mapping .............................................................. 5 1.6 Cortical maps defined by activity increases during task ................................... 5 1.7 Cortical networks defined by spontaneous activity ........................................... 6 1.8 Plasticity in functional cortex organization ....................................................... 7 1.9 Functional cortical reorganization in ischemic stroke ....................................... 9 1.10 Parallels between developmental critical periods and recovery after injury .... 11 1.11 Summary of findings ...................................................................................... 13 1.12 References .................................................................................................... 14 Chapter 2: Sensory Deprivation Following Focal Ischemia Accelerates Remapping and Improves Behavioral Recovery through Arc-Dependent Synaptic Plasticity ......... 28 2.1 Preface .......................................................................................................... 29 ii 2.2 Abstract ......................................................................................................... 30 2.3 Introduction ................................................................................................... 31 2.4 Results .......................................................................................................... 33 2.5 Discussion ..................................................................................................... 38 2.7 Methods ........................................................................................................ 43 2.8 Acknowledgements ....................................................................................... 50 2.9 Figures .......................................................................................................... 51 2.10 References .................................................................................................... 70 Chapter 3: Early visual experience modulates spatiotemporal relationships in infra-slow activity between distinct cortical regions through an Arc-dependent mechanism 77 3.1 Preface .......................................................................................................... 78 3.2 Abstract ......................................................................................................... 79 3.3 Introduction ................................................................................................... 80 3.4 Results .......................................................................................................... 82 3.5 Discussion ..................................................................................................... 89 3.6 Methods ........................................................................................................ 96 3.7 Acknowledgements ..................................................................................... 101 3.8 Figures ........................................................................................................ 103 3.9 References .................................................................................................. 112 Chapter 4: Electrically coupled inhibitory interneuron networks limit spontaneous activity coupling between distant cortical regions .............................................................. 123 iii 4.1 Preface ........................................................................................................ 124 4.2 Abstract ....................................................................................................... 125 4.3 Introduction ................................................................................................. 126 4.4 Results ........................................................................................................ 127 4.5 Discussion ................................................................................................... 131 4.6 Methods ...................................................................................................... 134 4.7 Acknowledgements ..................................................................................... 137 4.8 Figures ........................................................................................................ 138 4.9 References .................................................................................................. 146 Chapter 5: Conclusion .............................................................................................. 151 5.1 Summary of findings .................................................................................... 152 5.2 Cortical remapping as a modifiable therapeutic target ................................. 152 5.3 Relationship between task-evoked remapping and spontaneous activity ..... 153 5.4 Excitatory neuron mechanisms in cortical functional organization plasticity: a role for Arc ........................................................................................................................ 154 5.5 Electrically coupled inhibitory interneuron networks modulate cortical functional organization .......................................................................................................... 155 5.6 Tuning spontaneous activity correlation to the appropriate level .................. 156 Plasticizing the adult brain ..................................................................................... 156 5.7 Targeted facilitation of cortical plasticity with sensory deprivation ................ 157 5.8 Enhancing plasticity with direct cortical manipulation ................................... 158 iiii 5.9 Examining higher frequency content in functional organization relationships160 5.10 Concluding Remarks ................................................................................... 162 5.11 References .................................................................................................. 163 ivi List of Figures Chapter 2 Figure 2.1: Experimental design and timecourse .................................................... 51 Figure 2.2: Whisker deprivation accelerates S1FP remapping after photothrombosis ................................................................................................................................ 52 Figure 2.3: Right S1FP phothrombosis is functionally selective ............................... 53 Figure 2.4: Whisker deprivation accelerates and enhances behavioral recovery after S1FP photothrombosis ...................................................................................................... 54 Figure 2.5: Region of remapping demonstrates increased dendritic spine density ... 55 Figure 2.6: Experimental design and timecourse for whisker trimming and regrowth