Mechanisms involved in the norepinephrine-mediated protection of synapses from depotentiation

  • Author / Creator
    Rah, Sean S
  • Norepinephrine (NE) is a key neuromodulator that controls the longevity of synaptic plasticity such as long term potentiation (LTP). Activation of beta-adrenergic receptors (β-ARs) is known to boost persistence of LTP in area CA1 of mouse hippocampal slices. Activity-induced weakening (depotentiation, DPT) via 5Hz stimulation depresses the strength of synaptic transmission at synapses that have recently undergone LTP. I tested the hypothesis that NE primes synapses for subsequent long-lasting LTP, serving to protect potentiated synapses from depotentiation. Using population excitatory postsynaptic potential (EPSP) recordings from CA1 of mouse hippocampal slices, I show that NE (10uM) applied well before weak tetanic stimulation (1 x 100-Hz, 1s) protects synapses from depotentiation. This protection is no longer present when PKA and ERK (downstream protein kinases of the β-AR pathway) have been pharmacologically blocked. I also present evidence suggesting that, in addition to these kinases, NMDA receptors may also play a role in initiating the intracellular mechanisms that protect, or immunize, potentiated synapses from activity-induced weakening.

  • Subjects / Keywords
  • Graduation date
    Fall 2016
  • 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
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Ali, Declan (Physiology)
    • Dickson, Clayton (Psychology)
    • Gosgnach, Simon (Physiology)