Optogenetic Interrogation of Primary Visual Cortex and Its Impact on Neural Coding and Behavior
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The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 8-2017 Optogenetic interrogation of primary visual cortex and its impact on neural coding and behavior Ariana R. Andrei Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Behavioral Neurobiology Commons, and the Systems Neuroscience Commons Recommended Citation Andrei, Ariana R., "Optogenetic interrogation of primary visual cortex and its impact on neural coding and behavior" (2017). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 747. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/747 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. APPROVAL PAGE OPTOGENETIC INTERROGATION OF PRIMARY VISUAL CORTEX AND ITS IMPACT ON NEURAL CODING AND BEHAVIOR By Ariana R. Andrei, MSc APPROVED: ______________________________ Roger Janz, Ph.D. Advisory Professor ______________________________ John H. Byrne, Ph.D. ______________________________ Daniel J. Felleman, Ph.D. ______________________________ Dora Angelaki, Ph.D. ______________________________ John Spudich, Ph.D. APPROVED: ____________________________ Dean, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences TITLE PAGE OPTOGENETIC INTERROGATION OF PRIMARY VISUAL CORTEX AND ITS IMPACT ON NEURAL CODING AND BEHAVIOR A DISSERTATION Presented to the Faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY By Ariana R. Andrei, MSc Houston, Texas Date of Graduation (August,2017) ii DEDICATION For Gus MacCaully who introduced me to the dance of the universe iii ACKNOWLEDGEMENTS Sorin Pojoga, PhD began the collaborative effort between the Janz and Dragoi labs to implement extremely novel at the time optogenetic techniques in non-human primates. He designed the technical aspects of the laser stimulation, and the original computer codes used for the behavioral tasks. We worked together for several years collecting data, designing and redesigning experimental details, and analyzing the data most of which is presented in Chapter III. Sam Debes, BSc was closely involved in the GtACR- 2 experiments presented in Chapter IV, starting from the initial virus injections, to data collection, spike sorting and data analyses. Elsa Rodarte Rascon, MD & Xiaoqin Lin, PhD were responsible for the fixing, mounting and immunohistochemistry of the biopsied tissue presented in Chapter IV. Elsa performed the biopsy. Valentin Dragoi, PhD generously supplied his monkeys, laboratory space, key personnel and expertise for these studies. Roger Janz, PhD handled matters relating to virus construction and preparation in addition to his formal role of wisdom purveyor. I would also like to thank (in no particular order) the many people who provided critical input and stimulating conversations regarding this project over the years: Daniel Felleman, Jack Byne, John Spudich, Dora Angelaki, Michael Beierlein, Neda Shahidi, Ming Hu, Marcello Mulas, Russell Milton, and Mircea Chelaru. iv ABSTRACT OPTOGENETIC INTERROGATION OF PRIMARY VISUAL CORTEX AND ITS IMPACT ON NEURAL CODING AND BEHAVIOR By Ariana Ruxandra Andrei, Msc Advisory Professor: Roger Janz, Ph.D. Understanding the mechanism by which the brain transforms simple sensory inputs into rich perceptual experiences is one of the great mysteries of systems neuroscience. Undoubtedly this involves the activity of large populations of interconnected neurons, but while the responses of individual neurons to a variety of sensory stimuli have been well- characterized, how populations of such neurons organize their activity to create our sensory perceptions is almost entirely unknown. To investigate this complex circuitry requires the ability to causally manipulate the activity of neural populations and monitor the resultant effects. Here we focus on primary visual cortex (V1), which has been shown to be crucial for visual perception, and utilize optogenetic tools to render the activity of genetically- defined neural populations sensitive to light. By simultaneously recording and modulating (either driving or silencing) the activity of excitatory (glutamatergic) neurons, we are able to causally examine their role in visual perception. Here we report 3 major findings. First, we show that activating subpopulations of excitatory neurons can improve visual perception under certain conditions and that information in V1 used for perceptual decisions is integrated across spatially-limited populations of neurons. Further, we show that a key signature of this information integration is a reduction in correlated variability v between neurons. Correlated variability has been implicated as a major source of behavioral choice related activity in the cortex, and theorized to be a major factor limiting information in cortical populations. However, until now, there has not been a way to manipulate correlations without altering firing rates or other task related variables. Here we demonstrate a novel method using optogenetic stimulation to causally manipulate correlated variability between cortical neurons without altering their firing rates. Lastly, with the goal of expanding the currently limited repertoire of optogenetic tools for non- human primates, we establish the viability of a novel optogenetic construct capable of dramatically silencing neural populations using a recently discovered anion conducting channelrhodopsin. vi TABLE OF CONTENTS APPROVAL PAGE .................................................................................................................................. i TITLE PAGE ............................................................................................................................................. ii DEDICATION ............................................................................................................................................. iii ACKNOWLEDGEMENTS ....................................................................................................................... iv ABSTRACT................................................................................................................................................. v TABLE OF CONTENTS ......................................................................................................................... vii LIST OF FIGURES .................................................................................................................................. ix Preface ....................................................................................................................................................... x CHAPTER I: INTRODUCTION & BACKGROUND ......................................................................... 1 1.0 Introduction ................................................................................................................................... 1 1.1 Functional organization of early visual circuits ............................................................... 2 1.2 Gain control & surround modulation ....................................................................................... 7 1.3 Coding visual stimuli with neural population activity .................................................. 10 1.4 Stimulating cortical networks overview ............................................................................ 12 1.5 Hypotheses and Research Aims .......................................................................................... 16 CHAPTER II: METHODS ....................................................................................................................... 19 2.1 Animal subjects ........................................................................................................................... 19 2.2 Viral vector injections ................................................................................................................ 19 2.2.1 Channelrhodopsin-2 (ChR2) constuct ............................................................................ 19 2.2.2 Gt-ACR2 construct ............................................................................................................... 20 2.2.3 Cortical biopsy & immunohistochemistry ..................................................................... 21 2.3 Electrophysiological recordings ............................................................................................. 22 2.4 Delivering light to neurons ....................................................................................................... 23 2.5 Behavioral tasks .........................................................................................................................