Homeostatic plasticity of Intrinsic Excitability (PhD)

For the nervous system to function properly, activity levels must be regulated. Excitable cells operate in a regime that is responsive to normal levels of input but they also need to adjust their excitability to counter sustained changes in mean activity. Such changes in activity levels occur during development, and may also result from Hebbian learning. Neurophysiological correlates of Hebbian learning have been found to strengthen connectivity between excitatory cells in response to correlated firing patterns, and enhance intrinsic excitability at the same time [1]. In isolation, this constitutes a positive feedback loop which may destabilise network activity [3]. It is therefore likely that homeostatic mechanisms exist to co-regulate activity on a cellular level, and several candidate mechanisms have been characterised to date [2,3]. The majority of these studies have focussed on how neurons adapt to diminished levels of activity. In this project we study the opposite situation by asking the question, how do neurons respond to elevated input over a long timescale?


[1] Chavez-Noriega LE, Halliwell JV, Bliss TV (1990) A decrease in firing threshold observed after
induction of the EPSP-spike (E-S) component of long-term potentiation in rat hippocampal slices. Exp Brain
Res 79:633-641.
[2] Desai NS, Rutherford LC, Turrigiano GG (1999) Plasticity in the intrinsic excitability of cortical
pyramidal neurons. Nat Neurosci 2:515-520
[3] Turrigiano GG, Nelson SB (2004) Homeostatic plasticity in the developing nervous system. Nat Rev
Neurosci 5:97-107

Related Themes

Related Publications and Presentations

  • Timothy OLeary, Mark C W Van Rossum, and DJA Wyllie, “Homeostatic regulation of intrinsic excitability in hippocampal neurons: response to chronic depolarisation”, FENS Abstracts, 2008.
  • Timothy O’Leary, Mark C W Van Rossum, and David Wyllie, “Homeostasis of intrinsic excitability in hippocampal neurones: dynamics and mechanism of the response to chronic depolarization”, Journal of Physiology, 2010, 588, 157-170.
  • PE Chen, K Erreger, Timothy O’Leary, M Livesey, SF Traynelis, and DJA Wyllie, “Glycine potency among recombinant N-methyl-D-aspartate receptor subtypes is influenced by the S2 glutamate binding region of the NR2 subunit”, Society for Neuroscience (SfN), 2006.
  • Timothy O’Leary, Mark C W Van Rossum, and DJA Wyllie, “Conductance changes underlying homeostatic regulation of intrinsic excitability in hippocampal neurons”, Society for Neuroscience (SfN), Washington DC, 2008.
  • Adam Barrett, Richard Morris, Guy Billings, and Mark C W Van Rossum, “Biophysical Model of Long-Term Potentiation and Synaptic Tagging and Capture”, PLOS Computational Biology, 2008.

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