Spike-timing-dependent plasticity of inhibitory synapses in the entorhinal cortex

J Neurophysiol. 2006 Dec;96(6):3305-13. doi: 10.1152/jn.00551.2006. Epub 2006 Aug 23.

Abstract

Actions of inhibitory interneurons organize and modulate many neuronal processes, yet the mechanisms and consequences of plasticity of inhibitory synapses remain poorly understood. We report on spike-timing-dependent plasticity of inhibitory synapses in the entorhinal cortex. After pairing presynaptic stimulations at time t(pre) with evoked postsynaptic spikes at time t(post) under pharmacological blockade of excitation we found, via whole cell recordings, an asymmetrical timing rule for plasticity of the remaining inhibitory responses. Strength of response varied as a function of the time interval Deltat = t(post) - t(pre): for Deltat > 0 inhibitory responses potentiated, peaking at a delay of 10 ms. For Deltat < 0, the synaptic coupling depressed, again with a maximal effect near 10 ms of delay. We also show that changes in synaptic strength depend on changes in intracellular calcium concentrations and demonstrate that the calcium enters the postsynaptic cell through voltage-gated channels. Using network models, we demonstrate how this novel form of plasticity can sculpt network behavior efficiently and with remarkable flexibility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / physiology
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electrophysiology
  • Entorhinal Cortex / drug effects
  • Entorhinal Cortex / physiology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • Models, Neurological
  • Nerve Net / cytology
  • Nerve Net / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Nimodipine / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Seizures / physiopathology
  • Synapses / drug effects
  • Synapses / physiology*

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Chelating Agents
  • GABA Antagonists
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Egtazic Acid
  • Nimodipine
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Bicuculline