Mechanisms of Experience-Dependent Prevention of Plasticity in Visual Circuits

Mechanisms of Experience-Dependent Prevention of Plasticity in Visual Circuits

Georgia State University ScholarWorks @ Georgia State University Neuroscience Institute Dissertations Neuroscience Institute Summer 8-12-2014 Mechanisms of Experience-dependent Prevention of Plasticity in Visual Circuits Timothy Balmer Follow this and additional works at: https://scholarworks.gsu.edu/neurosci_diss Recommended Citation Balmer, Timothy, "Mechanisms of Experience-dependent Prevention of Plasticity in Visual Circuits." Dissertation, Georgia State University, 2014. https://scholarworks.gsu.edu/neurosci_diss/13 This Dissertation is brought to you for free and open access by the Neuroscience Institute at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Neuroscience Institute Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. MECHANISMS OF EXPERIENCE-DEPENDENT PREVENTION OF PLASTICITY IN VISUAL CIRCUITS by TIMOTHY S. BALMER Under the Direction of Sarah L. Pallas ABSTRACT Development of brain function is instructed by both genetically-determined processes (nature) and environmental stimuli (nurture). The relative importance of nature and nurture is a major question in developmental neurobiology. In this dissertation, I investigated the role of visual experience in the development and plasticity of the visual pathway. Each neuron that receives visual input responds to a specific area of the visual field- their receptive field (RF). Developmental refinement reduces RF size and underlies visual acuity, which is important for survival. By rearing Syrian hamsters ( Mesocricetus auratus ) in constant darkness (dark rearing, DR) from birth, I investigated the role of visual experience in RF refinement and plasticity. Previous work in this lab has shown that developmental refinement of RFs occurs in the absence of visual experience in the superior colliculus (SC), but that RFs unrefine and thus enlarge in adulthood during chronic DR. Using an in vivo electrophysiological approach, I show that, contrary to a widely held view, visual experience is not necessary for refinement of RFs in primary visual cortex (V1). In both SC and V1, RFs refine by postnatal day (P) 60, but enlarge by P90 with chronic DR. One week of visual experience was sufficient to prevent RF enlargement in SC and V1. How normal sensory experience prevents plasticity in mature circuits is not well understood. Using an in vitro electrophysiological approach, I demonstrated that GABAergic inhibition is reduced in DR SC, which in turn affects short-term (but not long-term) synaptic plasticity. The level of GABA BR-mediated short-term synaptic depression (STD) that occurs during high-frequency afferent stimulation, such as occurs during vision, is reduced by DR. Using a computational model of RF size, I propose that, in addition to the effect of reduced inhibition, reduced STD of excitation could contribute to enlarged RFs. This work provides insight into mechanisms of development and plasticity of the nervous system. How plasticity is restricted in mature circuits is of fundamental importance in neuroscience and could instruct therapies to prevent maladaptive plasticity in disease and to enhance recovery of function in adults. INDEX WORDS: Superior colliculus, Visual cortex, Adult plasticity, Receptive field, Inhibitory plasticity, Rodent, Critical period, Visual deprivation MECHANISMS OF EXPERIENCE-DEPENDENT PREVENTION OF PLASTICITY IN VISUAL CIRCUITS by TIMOTHY S. BALMER A Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the College of Arts and Sciences Georgia State University 2014 Copyright by Timothy Seth Balmer 2014 MECHANISMS OF EXPERIENCE-DEPENDENT PREVENTION OF PLASTICITY IN VISUAL CIRCUITS by TIMOTHY S. BALMER Committee Chair: Sarah L. Pallas Committee: Paul S. Katz Vincent Rehder Peter Wenner Electronic Version Approved: Office of Graduate Studies College of Arts and Sciences Georgia State University August 2014 iv ACKNOWLEDGEMENTS This work would not have been possible without the advice and support of my dissertation committee: Profs. Peter Wenner, Paul Katz, Vincent Rehder, and my mentor, Sarah Pallas. I also thank members of the Pallas lab for useful discussions and the animal care staff for maintaining the dark reared hamsters. I am grateful for the patience and support of my family and friends, particularly my lovely wife. v TABLE OF CONTENTS ACKNOWLEDGEMENTS .................................................................................................................. iv LIST OF FIGURES ............................................................................................................................... xi 1 INTRODUCTION ............................................................................................................................. 1 1.1 Nervous system development and plasticity ................................................................. 2 1.1.1 Visual system as a model of nervous system development and plasticity .................. 2 1.1.2 General organization of the mammalian subcortical and cortical visual systems ... 3 1.1.3 Activity-independent factors in visual system development ....................................... 4 1.1.4 Activity-dependent factors in visual system development .......................................... 6 1.1.5 Role of activity in RF refinement in SC ................................................................... 11 1.1.6 Role of activity in development of RF properties in V1 ........................................... 13 1.1.7 Proposed mechanisms of RF maintenance .............................................................. 15 1.2 Why study Syrian hamsters? ....................................................................................... 17 1.3 Clinical relevance .......................................................................................................... 18 1.4 Specific aims of dissertation ......................................................................................... 18 2 REFINEMENT BUT NOT MAINTENENCE OF VISUAL RECEPTIVE FIELDS IS INDEPENDENT OF VISUAL EXPERIENCE .................................................................................. 20 2.1 Abstract .......................................................................................................................... 21 2.2 Introduction ................................................................................................................... 22 2.3 Materials and Methods ................................................................................................. 25 2.3.1 Animals and rearing conditions ............................................................................... 25 2.3.2 Surgery ...................................................................................................................... 25 vi 2.3.3 Electrophysiology ...................................................................................................... 26 2.3.4 Visual stimulus presentation..................................................................................... 26 2.3.5 Analysis of RFs ......................................................................................................... 27 2.3.6 Putative excitatory and inhibitory unit classification .............................................. 27 2.3.7 Statistical analyses .................................................................................................... 28 2.4 Results ............................................................................................................................ 29 2.4.1 Dark rearing to P60 does not prevent RF refinement in V1 ................................... 29 2.4.2 Dark rearing to P90 caused a failure to maintain RF refinement in V1 ................ 30 2.4.3 One week but not 3 days of late juvenile visual experience was sufficient to maintain refined RFs in V1 .................................................................................................. 32 2.4.4 Type of visual stimulus did not influence RF width measurements in V1.............. 34 2.4.5 DR increased spontaneous activity in V1 ................................................................. 38 2.4.6 Both putative excitatory and putative inhibitory V1 units fail to maintain refined RFs ................................................................................................................................... 40 2.4.7 Late but not early juvenile visual experience was sufficient to maintain refined RFs in SC .............................................................................................................................. 42 2.4.8 Early juvenile visual experience that is not sufficient to maintain RFs does not prevent RF refinement in SC ................................................................................................ 46 2.5 Discussion ....................................................................................................................... 47 2.5.1 Spontaneous retinal activity is sufficient to refine SC and V1 RFs ........................ 48 2.5.2 V1 requires different timing of light exposure than SC to prevent deprivation- induced plasticity ................................................................................................................... 48 vii 2.5.3 The shape of enlarged RFs was maintained in SC .................................................

View Full Text

Details

  • File Type
    pdf
  • Upload Time
    -
  • Content Languages
    English
  • Upload User
    Anonymous/Not logged-in
  • File Pages
    159 Page
  • File Size
    -

Download

Channel Download Status
Express Download Enable

Copyright

We respect the copyrights and intellectual property rights of all users. All uploaded documents are either original works of the uploader or authorized works of the rightful owners.

  • Not to be reproduced or distributed without explicit permission.
  • Not used for commercial purposes outside of approved use cases.
  • Not used to infringe on the rights of the original creators.
  • If you believe any content infringes your copyright, please contact us immediately.

Support

For help with questions, suggestions, or problems, please contact us