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Modulation of dendritic excitability Open Access


Other title
neuropeptide Y
long-term potentiation
Synaptic plasticity
Type of item
Degree grantor
University of Alberta
Author or creator
Hamilton, Trevor
Supervisor and department
Colmers, William F. (Pharmacology)
Examining committee member and department
Dickson, Clayton (Psychology)
Smith, Peter A. (Pharmacology)
Wang, Yu Tian (UBC)
Ballanyi, Klaus (Physiology)
Centre for Neuroscience

Date accepted
Graduation date
Doctor of Philosophy
Degree level
The computational ability of principal neurons and interneurons in the brain and their ability to work together in concert are thought to underlie higher order cognitive processes such as learning, memory, and attention. Dendrites play a very important role in neuronal information processing because they receive and integrate incoming input and can undergo experience-dependent changes that will alter the future output of the neuron. Here, I have used whole-cell patch clamp recordings and fluorescent Ca2+-imaging to examine the modulation of dendritic excitability in principal neurons of the rat and human hippocampus and neocortex. First, I determined that dendrites of dentate granule cells of the hippocampus are tuned to high frequencies of both afferent input and backpropagating action potentials. Under these conditions they are also capable of generating regenerative dendritic activity that can propagate to the soma, which is prone to modulation. In particular, Neuropeptide Y (NPY) Y1 receptors can decrease frequency-dependent dendritic Ca2+ influx. Dopamine D1 receptors (D1Rs) have an opposite effect; they potentiate frequency-dependent dendritic excitability. These two neuromodulators also have an opposing effect on plasticity, with dopamine acting to induce, and NPY acting to inhibit long-term potentiation (LTP). Parallel observations of D1-induced LTP and an NPY-mediated decrease in dendritic excitability in rodents were complemented by findings in human dentate granule cells. Second, I examined the role of NPY receptors on dendrites of layer 5 pyramidal neurons. In these neurons I found that NPY acts post-synaptically on distal dendrites via the Y1 receptor to inhibit frequency-dependent Ca2+-currents, similar to the findings in dentate granule cells. NPY also decreased regenerative Ca2+ currents caused by the appropriate pairing of pre- and post-synaptic input. Together, these observations demonstrate that the role of NPY in the hippocampus and neocortex is not solely as an anti-epileptic agent. NPY release, likely to occur during high frequency oscillatory activity, can act locally to limit dendritic excitability, which can have a profound effect on plasticity. In the dentate gyrus, NPY can inhibit a D1R induced increased dendritic excitability and resultant changes in synaptic strength. These findings will further the understanding of dendritic information processing in the hippocampus and neocortex.
License granted by Trevor Hamilton ( on 2009-09-28T17:53:46Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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