University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Cortical Mechanisms Of Adaptation In Auditory Processing Ryan Natan University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Neuroscience and Neurobiology Commons Recommended Citation Natan, Ryan, "Cortical Mechanisms Of Adaptation In Auditory Processing" (2017). Publicly Accessible Penn Dissertations. 2498. https://repository.upenn.edu/edissertations/2498 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2498 For more information, please contact [email protected]. Cortical Mechanisms Of Adaptation In Auditory Processing Abstract Adaptation is computational strategy that underlies sensory nervous systems’ ability to accurately encode stimuli in various and dynamic contexts and shapes how animals perceive their environment. Many questions remain concerning how adaptation adjusts to particular stimulus features and its underlying mechanisms. In Chapter 2, we tested how neurons in the primary auditory cortex adapt to changes in stimulus temporal correlation. We used chronically implanted tetrodes to record neuronal spiking in rat primary auditory cortex during exposure to custom made dynamic random chord stimuli exhibiting different levels of temporal correlation. We estimated linear non-linear model for each neuron at each temporal correlation level, finding that neurons compensate for temporal correlation changes through gain-control adaptation. This experiment extends our understanding of how complex stimulus statistics are encoded in the auditory nervous system. In Chapter 3 and 4, we tested how interneurons are involved in adaptation by optogenetically suppressing parvalbumin-positive (PV) and somatostatin- positive (SOM) interneurons during tone train stimuli and using silicon probes to record neuronal spiking in mouse primary auditory cortex. In Chapter 3, we found that inhibition from both PVs and SOMs contributes to stimulus-specific adaptation (SSA) through different mechanisms. SOM inhibition was stimulus-specific, suppressing responses to standard tones more strongly than responses to deviant tones, and increasing with standard tone repetition. PVs amplified SSA because inhibition was similar for standard and deviant tones and PV mediated inhibition was insensitive to tone repetition. PVs and SOMs themselves exhibit SSA, and a Wilson-Cowan dynamic model identified that PVs and SOMs can directly contribute to SSA in pyramidal neurons. In Chapter 4, we tested how SOMs and PVs inhibition is modulated with the dynamics of adaptation and across frequency tuning, during exposure to single frequency tone trains across the neuron’s tuning curve. We found that the magnitude of SOM inhibition correlated with the magnitude of adaptive suppression, while PVs inhibition was largely insensitive to stimulus conditions. Together Chapters 3 and 4 implicate SOM inhibition in actively suppressing responses in a stimulus-specific manner while PV inhibition may passively enhance stimulus-specific suppression. These experiments inform the underlying principles and mechanisms of cortical sensory adaptation. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Neuroscience First Advisor Maria N. Geffen Keywords Adaptation, Auditory, Cortex, Inhibition, Interneuron Subject Categories Neuroscience and Neurobiology This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/2498 CORTICAL MECHANISMS OF ADAPTATION IN AUDITORY PROCESSING Ryan G Natan A DISSERTATION In Neuroscience Presented to the Faculties of the University of Pennsylvania In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2017 Supervisor of Dissertation ________________________ Maria Neimark Geffen, PhD Assistant Professor of Otorhinolaryngology Graduate Group Chairperson ________________________ Joshua I. Gold, PhD Professor of Neuroscience Dissertation Committee Yale Cohen, Associate Professor of Otorhinolaryngology Diego Contreras, Professor of Neuroscience Christopher Fang-Yen, Assistant Professor of Neuroscience Robert Froemke, Assistant Professor of Otolaryngology, Physiology & Neuroscience, NYU This dissertation is dedicated to my family. I simply could not have achieved my goals without the boundless love and support of my mother, father, brother, and especially my wife Kathy. Thanks, I love you! ii ACKNOWLEDGMENTS I would like to express my utmost gratitude to my advisor, Maria Neimark Geffen, for providing fantastic mentorship in my education, lab work and scientific career. It has been a wonderful experience to learn and grow under the guidance of a genuine friend and inspiring individual. Thanks to Yale Cohen, Diego Contreras, Chris Fang-Yen and Robert Froemke for serving on my thesis committee and helping me make the most of my graduate training. Thanks in addition to Mark Aizenberg, Jennifer Blackwell, John Briguglio, Isaac Carruthers, Laetitia Mwilambwe- Tshilobo, Winnie Rao, and current and former members of the Geffen Lab – it has been a great pleasure working with you. Thanks finally to the students, faculty and administration of the Neuroscience Graduate Group, who have cultivated a uniquely rewarding graduate training experience. iii ABSTRACT CORTICAL MECHANISMS OF ADAPTATION IN AUDITORY PROCESSING Ryan G Natan Maria Neimark Geffen Adaptation is computational strategy that underlies sensory nervous systems’ ability to accurately encode stimuli in various and dynamic contexts and shapes how animals perceive their environment. Many questions remain concerning how adaptation adjusts to particular stimulus features and its underlying mechanisms. In Chapter 2, we tested how neurons in the primary auditory cortex adapt to changes in stimulus temporal correlation. We used chronically implanted tetrodes to record neuronal spiking in rat primary auditory cortex during exposure to custom made dynamic random chord stimuli exhibiting different levels of temporal correlation. We estimated linear non-linear model for each neuron at each temporal correlation level, finding that neurons compensate for temporal correlation changes through gain-control adaptation. This experiment extends our understanding of how complex stimulus statistics are encoded in the auditory nervous system. In Chapter 3 and 4, we tested how interneurons are involved in adaptation by optogenetically suppressing parvalbumin-positive (PV) and somatostatin- positive (SOM) interneurons during tone train stimuli and using silicon probes to record neuronal spiking in mouse primary auditory cortex. In Chapter 3, we found that inhibition from both PVs and SOMs contributes to stimulus-specific adaptation (SSA) through different mechanisms. SOM inhibition was stimulus-specific, suppressing iv responses to standard tones more strongly than responses to deviant tones, and increasing with standard tone repetition. PVs amplified SSA because inhibition was similar for standard and deviant tones and PV mediated inhibition was insensitive to tone repetition. PVs and SOMs themselves exhibit SSA, and a Wilson-Cowan dynamic model identified that PVs and SOMs can directly contribute to SSA in pyramidal neurons. In Chapter 4, we tested how SOMs and PVs inhibition is modulated with the dynamics of adaptation and across frequency tuning, during exposure to single frequency tone trains across the neuron’s tuning curve. We found that the magnitude of SOM inhibition correlated with the magnitude of adaptive suppression, while PVs inhibition was largely insensitive to stimulus conditions. Together Chapters 3 and 4 implicate SOM inhibition in actively suppressing responses in a stimulus-specific manner while PV inhibition may passively enhance stimulus-specific suppression. These experiments inform the underlying principles and mechanisms of cortical sensory adaptation. v TABLE OF CONTENTS DEDICATIONS ...................................................................................................................... II ACKNOWLEDGMENTS ........................................................................................................ III ABSTRACT ........................................................................................................................... IV TABLE OF CONTENTS.......................................................................................................... VI LIST OF FIGURES ............................................................................................................... VIII 1. INTRODUCTION ............................................................................................................... 1 The roles of adaptation in auditory sensation ................................................................................................ 2 Adaptation in models of sensory encoding ..................................................................................................... 8 Inhibitory interneurons ................................................................................................................................. 11 Inhibition in adaptation ................................................................................................................................. 14 Bibliography .................................................................................................................................................. 18