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Alterations to the Membrane Properties of CA1 Pyramidal Neurons by the Amnestic Agent Anisomycin

  • Author / Creator
    LeBlancq, Michelle J
  • The notion that long-term memory is dependent upon the production of new proteins is a near-axiomatic assertion in the field of behavioural neuroscience. The idea that protein synthesis is required for long-term memory formation and maintenance is based largely on the amnestic effects of protein synthesis inhibitors such as anisomycin (ANI). One issue with this hypothesis, however, is that protein synthesis inhibitors have been shown to alter other aspects of neurobiological functioning. Previous work from our lab has shown an impairment of neural activity and functional integrity of the hippocampus following intracerebral infusions of ANI. We therefore sought to investigate how protein synthesis inhibition using ANI might affect passive and active membrane properties of hippocampal CA1 principal neurons. Firstly, we used radiolabelled amino-acid incorporation to confirm that a short (30 minute), low concentration (100 µM) bath application of ANI to acute transverse hippocampal slices was sufficient to produce an inhibition of protein synthesis, and observed an approximately 45% decrease in amino acid incorporation. Secondly, bath application of anisomycin on CA1 pyramidal cells recorded via whole-cell patch-clamp configuration showed that ANI caused a reduction in membrane polarization and detrimentally affected firing properties, without any changes in input resistance, membrane time constant, or threshold to elicit an action potential. Lastly, this pattern of results suggested that anisomycin might be disrupting mitochondrial activity, which was confirmed using a marker of electron transport; 2,3,5-triphenyltetrazolium chloride (TTC). Overall, these findings further the knowledge of how agents such as ANI may produce impairments of neural activity (as well as amnesia), and extend caution toward the evaluation of behavioural responses to molecular manipulations without considering effects on cellular and network function in the nervous system.

  • Subjects / Keywords
  • Graduation date
    2017-06:Spring 2017
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Centre for Neuroscience
  • Supervisor / co-supervisor and their department(s)
    • Hamilton, Trevor J (Department of Psychology MacEwan University, Neuroscience and Mental Health Institute)
    • Dickson, Clayton T (Department of Psychology, Neuroscience and Mental Health Institute, Department of Physiology)
  • Examining committee members and their departments
    • Gosgnach, Simon (Department of Physiology, Neuroscience and Mental Health Institute)
    • Funk, Gregory D (Department of Physiology, Neuroscience and Mental Health Institute)
    • Ali, Declan W (Department of Biological Sciences, Neuroscience and Mental Health Institute)