title: Intracellular correlate of EPSP-spike potentiation in CA1 pyramidal neurons is controlled by GABAergic modulation.
abstract: 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 gamma-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.
authors: Department of Neurobiology and Physiology, Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208, USA.
authors: Nathan P
authors: NP
authors: Staff
authors: Nelson
authors: N
authors: Spruston
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid