Intracellular correlate of EPSP-Spike potentiation in CA1 pyramidal neurons is controlled by GABAergic modulation

Nathan P. Staff, Nelson Spruston

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


The hippocampus has been used extensively as a model to study plastic changes in the brain's neural circuitry. Immediately after high-frequency stimulation to hippocampal Schaffer collateral axons, a dramatic change occurs in the relationship between the presynaptic CA3 and the postsynaptic CA1 pyramidal neurons. For a fixed excitatory postsynaptic potential (EPSP), there arises an increased likelihood of action potential generation in the CA1 pyramidal neuron. This phenomenon is called EPSP-spike (E-S) potentiation. We explored E-S potentiation, using patch-clamp techniques in the hippocampal slice preparation. A specific protocol was developed to measure the action potential probability for a given synaptic strength, which allowed us to quantify the amount of E-S potentiation for a single neuron. E-S potentiation was greatest when γ-aminobutyric acid (GABA)ergic inhibition was intact, suggesting that modulation of inhibition is a major aspect of E-S potentiation. Expression of E-S potentiation also correlated with a reduced action-potential threshold, which was greatest when GABAergic inhibition was intact. Conditioning stimuli produced a smaller threshold reduction when inhibition was blocked, but some reduction also occurred in the absence of a conditioning stimulus. Together, these results suggest that E-S potentiation is caused primarily through a reduction of GABAergic inhibition, leading to larger EPSPs and reduced action potential threshold. Our findings do not rule out, however, the possibility that modulation of voltage-gated conductances also contributes to E-S potentiation.

Original languageEnglish (US)
Pages (from-to)801-805
Number of pages5
Issue number7
StatePublished - 2003


  • Dialysis
  • Excitability
  • Hippocampus
  • Patch-clamp recording
  • Plasticity

ASJC Scopus subject areas

  • Cognitive Neuroscience


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