A cellular correlate of learning-induced metaplasticity in the hippocampus

Cereb Cortex. 2006 Apr;16(4):460-8. doi: 10.1093/cercor/bhi125. Epub 2005 Jun 15.


Metaplasticity, the plasticity of synaptic plasticity, is thought to have a pivotal role in activity-dependent modulation of synaptic connectivity, which underlies learning and memory. Metaplasticity is usually attributed to modifications in glutamate receptor-mediated synaptic transmission. However, experimental evidence and theoretical considerations suggest that learning reduces the predisposition for further synaptic strengthening, while behavioral studies show that learning capability is enhanced by prior learning. Here we show that enhanced neuronal excitability in CA1 pyramidal neurons, but not enhanced synaptic transmission, occurs prior to rule learning of an olfactory discrimination task. This transient enhancement lasts for 1 day after rule learning, is apparent throughout the cell population and results from reduction in the medium and slow after-hyperpolarizations that control spike frequency adaptation. Such olfactory learning-induced increased excitability in hippocampal neurons enhances the rats' learning capability in another hippocampus-dependent task, the Morris water maze. Once olfactory discrimination rule learning is acquired, its maintenance is not dependent on the reduced post-burst AHP in hippocampal neurons. However, the enhanced spatial learning capability of olfactory-trained rats in the water maze is diminished once the post burst AHP in CA1 pyramidal cells resumes its initial value. We suggest that enhanced excitability of CA1 neurons may serve as a mechanism for generalized enhancement of hippocampus-dependent learning capability. In the presence of such enhanced neuronal excitability, the hippocampal network enters into a 'learning mode' in which a variety of hippocampus-dependent skills are acquired rapidly and efficiently.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Discrimination Learning / physiology*
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / physiology*
  • Male
  • Neuronal Plasticity / physiology*
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Smell / physiology*
  • Statistics as Topic
  • Synaptic Transmission / physiology*